a-methapred
Generic Name: (
Methylprednisolone Sodium Succinate)
Dosage Type: injection, solution Organization: HOSPIRA, INC.
(METHYLPREDNISOLONE SODIUM
SUCCINATE
FOR INJECTION, USP)
For Intravenous
or Intramuscular Use
Rx only
DESCRIPTION
Methylprednisolone Sodium Succinate, USP, an adrenocortical-like
steroid, is the sodium succinate ester of methylprednisolone.
It
occurs as a white, or nearly white, odorless hygroscopic amorphous solid.
Methylprednisolone sodium succinate is extremely soluble in water and is especially
well suited for intravenous use in situations in which high blood levels of
methylprednisolone are required rapidly.
Methylprednisolone
Sodium Succinate, USP is chemically designated 11ß,17,21-Trihydroxy-6a-methylpregna-1,4-diene-3,20-dione21-(sodium succinate). The structural formula is represented below:
A-METHAPRED (Methylprednisolone Sodium Succinate for Injection,
USP) for intravenous or intramuscular use is available as:
40 mg Univial®— Each 1
mL (when mixed) contains methylprednisolone sodium succinate equivalent to
methylprednisolone 40 mg; monobasic sodium phosphate, anhydrous 1.6 mg; dibasic
sodium phosphate, anhydrous 17.5 mg; lactose, anhydrous 25 mg and benzyl alcohol
9 mg added as preservative.
125
mg Univial— Each 2 mL (when mixed) contains methylprednisolone
sodium succinate equivalent to methylprednisolone 125 mg; monobasic sodium
phosphate, anhydrous 1.6 mg; dibasic sodium phosphate, anhydrous 17.4 mg and
benzyl alcohol 18 mg added as preservative.
May contain
sodium hydroxide and/or hydrochloric acid for pH adjustment.
NOTE: The 40 mg and 125 mg Univial should be used within
48 hours after reconstitution. Store at 20 to 25°C (68 to 77°F).
[See USP Controlled Room Temperature.] Avoid freezing. Refrigeration not required.
IMPORTANT
Therecommended diluent is Bacteriostatic Water for Injection, USP with 0.9% benzyl
alcohol (9 mg/mL benzyl alcohol).
A-METHAPRED is
prepared as a solution and lyophilized in its final container.
CLINICAL PHARMACOLOGY
Methylprednisolone is a potent anti-inflammatory steroid.
It has a greater anti-inflammatory potency than prednisolone and even less
tendency than prednisolone to induce sodium and water retention.
Methylprednisolone
sodium succinate has the same metabolic and anti-inflammatory actions as methylprednisolone.
When given parenterally and in equimolar quantities, methylprednisolone sodium
succinate and methylprednisolone are equivalent in biologic activity. The
relative potency of methylprednisolone sodium succinate and hydrocortisone
sodium succinate, as indicated by depression of eosinophil count, following
intravenous administration, is at least four to one. This is in good agreement
with the relative oral potency of methylprednisolone and hydrocortisone.
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, A-METHAPRED (methylprednisolone sodium
succinate) is indicated for intravenous or intramuscular use in the following
conditions:
-
Endocrine disorders:
a. 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).
b. Acute adrenocortical insufficiency (hydrocortisone
or cortisone is the drug of choice; mineralocorticoid supplementation may
be necessary, particularly when synthetic analogs are used).
c. Preoperatively and in the event of serious trauma
or illness, in patients with known adrenal insufficiency or when adrenocortical
reserve is doubtful.
d. Shock
unresponsive to conventional therapy if adrenocortical insufficiency exists
or is suspected.
e. Congenital
adrenal hyperplasia.
f. Hypercalcemia
associated with cancer.
g.Nonsuppurative thyroiditis.
-
Rheumatic disorders—
As adjunctive therapy for short-term administration (to tide the patient over
an acute episode or exacerbation) in:
a.Post-traumatic osteoarthritis.
b.Synovitis of osteoarthritis.
c.Rheumatoid arthritis, including juvenile rheumatoid arthritis (selected
cases may require low-dose maintenance therapy).
d. Acute and subacute bursitis.
e. Epicondylitis.
f. Acute nonspecific tenosynovitis.
g. Acute gouty arthritis.
h. Psoriatic arthritis.
i. Ankylosing spondylitis.
-
Collagen diseases—
During an exacerbation or as maintenance therapy in selected cases of:
a. Systemic lupus erythematosus.
b. Systemic dermatomyositis (polymyositis).
c. Acute rheumatic carditis.
-
Dermatologic diseases:
a. Pemphigus.
b.Severe erythema multiforme (Stevens-Johnson syndrome).
c. Exfoliative dermatitis.
d. Bullous dermatitis herpetiformis.
e. Severe seborrheic dermatitis.
f. Severe psoriasis.
g. Mycosis fungoides.
-
Allergic states—
Control of severe or incapacitating allergic conditions intractable to adequate
trials of conventional treatment in:
a.Bronchial asthma.
b.Contact dermatitis.
c.Atopic dermatitis.
d.Serum sickness.
e.Seasonal or perennial allergic rhinitis.
f. Drug hypersensitivity reactions.
g. Urticarial transfusion reactions.
h. 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:
a. Herpes
zoster ophthalmicus.
b. Iritis
iridocyclitis.
c. Chorioretinitis.
d. Diffuse posterior uveitis and choroiditis.
e. Optic neuritis.
f. Sympathetic ophthalmia.
g. Anterior segment inflammation.
h. Allergic conjunctivitis.
i. Allergic corneal marginal ulcers.
j. Keratitis.
-
Gastrointestinal diseases—
To tide the patient over a critical period of disease in:
a. Ulcerative colitis — (Systemic therapy).
b. Regional enteritis — (Systemic therapy).
-
Respiratory diseases:
a. Symptomatic sarcoidosis.
b. Berylliosis.
c. Fulminating or disseminated pulmonary tuberculosis
when concurrently accompanied by appropriate antituberculous chemotherapy.
d. Loeffler’s syndrome not manageable by
other means.
e. Aspiration
pneumonitis.
-
Hematologic disorders:
a. Acquired (autoimmune) hemolytic anemia.
b. Idiopathic thrombocytopenic purpura in adults
(IV only; IM administration is contraindicated).
c. Secondary thrombocytopenia in adults.
d. Erythroblastopenia (RBC anemia).
e. Congenital (erythroid) hypoplastic anemia.
-
Neoplastic diseases—
For palliative management of:
a.Leukemias and lymphomas in adults.
b. Acute leukemia of childhood.
-
Edematous state—
To induce diuresis or remission of proteinuria in the nephrotic syndrome,
without uremia, of the idiopathic type or that due to lupus erythematosus.
-
Nervous system:
a. Acute exacerbations of multiple sclerosis.
-
Miscellaneous:
a. Tuberculous meningitis with subarachnoid block
or impending block when used concurrently with appropriate antituberculous
chemotherapy.
b. Trichinosis
with neurologic and myocardial involvement.
CONTRAINDICATIONS
The use of methylprednisolone sodium succinate for injection
is contraindicated in premature infants because benzyl alcohol, a preservative
contained in Bacteriostatic Water for Injection used to reconstitute this
product, has been reported to be associated with fatal “Gasping Syndrome”
in premature infants. Methylprednisolone sodium succinate for injection is
also contraindicated in systemic fungal infections and patients with known
hypersensitivity to the product and its constituents.
WARNINGS
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.
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.
A study has failed to establish the efficacy
of methylprednisolone sodium succinate in the treatment of sepsis syndrome
and septic shock. The study also suggests that treatment of these conditions
with methylprednisolone may increase the risk of mortality in certain patients
(i.e., patients with elevated serum creatinine levels or patients who develop
secondary infections after methylprednisolone).
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
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.
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 on high dose, because of possible
hazards of neurological complications and a lack of antibody response.
The
use of A-METHAPRED (methylprednisolone sodium succinate) 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 anaphylactic (e.g., bronchospasm) 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.
There are reports
of cardiac arrhythmias and/or circulatory collapse and/or cardiac arrest following
the rapid administration of large IV doses of methylprednisolone sodium succinate
(greater than 500 mg administered over a period of less than 10 minutes).
Bradycardia has been reported during or after the administration of large
doses of methylprednisolone sodium succinate and may be unrelated to the speed
or duration of the infusion.
PRECAUTIONS
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 because of possible 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 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 pyrogenic infection;
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 observed.
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 corticosteroids
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 section).
Since
complications of treatment with glucocorticoids are dependent on the size
of the dose and the duration of treatment, a risk/benefit decision must be
made in each individual case as to dose and duration of treatment and as to
whether daily or intermittent therapy should be used.
Convulsions
have been reported with concurrent use of methylprednisolone and cyclosporin.
Since concurrent use of these agents results in a mutual inhibition of metabolism,
it is possible that adverse events associated with the individual use of either
drug may be more apt to occur.
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.
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
-
Severe arthralgia
-
Vertebral compression fractures
-
Aseptic necrosis of femoral and humeral heads
-
Pathologic fracture of long bones
-
Osteoporosis
Gastrointestinal
-
Peptic ulcer with possible 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
-
Increased intracranial pressure with papilledema (pseudotumor
cerebri) usually after treatment
-
Convulsions
-
Vertigo
-
Headache
Endocrine
-
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
-
Menstrual irregularities
-
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:
-
Hyperpigmentation or hypopigmentation
-
Subcutaneous and cutaneous atrophy
-
Sterile abscess
-
Anaphylactic reaction with or without circulatory collapse,
cardiac arrest, bronchospasm
-
Urticaria
-
Nausea and vomiting
-
Cardiac arrhythmias, hypotension or hypertension
DOSAGE AND ADMINISTRATION
When high dose therapy is desired, the recommended dose of
methylprednisolone sodium succinate is 30 mg/kg administered intravenously
over at least 30 minutes. This dose may be repeated every 4 to 6 hours
for 48 hours.
In general high dose corticosteroid therapy
should be continued only until the patient’s condition has stabilized;
usually not beyond 48 to 72 hours.
Although adverse
effects associated with high dose short-term corticoid therapy are uncommon,
peptic ulceration may occur. Prophylactic antacid therapy may be indicated.
In
other indications initial dosage will vary from 10 to 40 mg of methylprednisolone
depending on the clinical problem being treated. The larger doses may be required
for short-term management of severe, acute conditions. The initial dose usually
should be given intravenously over a period of several minutes. Subsequent
doses may be given intravenously or intramuscularly at intervals dictated
by the patient’s response and clinical condition. Corticoid therapy
is an adjunct to, and not replacement for, conventional therapy.
Dosage
may be reduced for infants and children but should be governed more by the
severity of the condition and response of the patient than by age or size.It should not be less than 0.5 mg/kg every 24 hours.
Dosage
must be decreased or discontinued gradually when the drug has been administered
for more than a few days. If a period of spontaneous remission occurs in a
chronic condition, treatment should be discontinued. Routine laboratory studies,
such as urinalysis, two-hour postprandial blood sugar, determination of blood
pressure and body weight, and a chest x-ray should be made at regular intervals
during prolonged therapy. Upper GI x-rays are desirable in patients with an
ulcer history or significant dyspepsia.
Methylprednisolone
sodium succinate for injection may be administered by intravenous or intramuscular
injection or by intravenous infusion, the preferred method for initial emergency
use being intravenous injection. To administer by intravenous (or intramuscular)
injection, prepare solution as directed. The desired dose may be administered
intravenously over a period of several minutes.
To prepare
solutions for intravenous infusion, first prepare the solution for injection
as directed. This solution may then be added to indicated amounts of Dextrose
Injection 5%, USP, Sodium Chloride Injection 0.9%, USP, or Dextrose 5% and
Sodium Chloride 0.9% Injection, USP.
Multiple
Sclerosis
In treatment of acute exacerbations
of multiple sclerosis, daily doses of 200 mg of prednisolone for a week followed
by 80 mg every other day for 1 month have been shown to be effective (4 mg
of methylprednisolone is equivalent to 5 mg of prednisolone).
PREPARATION OF SOLUTIONS
Univials:
-
Remove protective cap, give the plunger-stopper a quarter
turn and press to force diluent into the lower compartment.
-
Agitate immediately to effect solution. The Univial should
be agitated in a manner which insures mixing throughout both compartments.
-
Use solutions in 40 mg and 125 mg Univials within 48 hours.
-
Sterilize top of plunger-stopper with a suitable germicide.
-
Invert vial. Insert needle squarely through center of plunger-stopper
until tip is just visible. Withdraw dose.
Storage: The 40 mg and
125 mg Univial should be used within 48 hours after reconstitution. After
reconstitution, store at 20 to 25°C (68 to 77°F). [See USP Controlled
Room Temperature.] Avoid freezing. Refrigeration not required.
Parenteral
drug products should be inspected visually for particulate matter and discoloration
prior to administration, whenever solution and container permit.
HOW SUPPLIED
Sterile A-METHAPRED (methylprednisolone sodium succinate
for injection, USP) is supplied as follows:
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LIST
NO.
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CONTAINER
TYPE
|
DOSE/VOLUME
PROVIDED
|
CONCENTRATION
AFTER
RECONSTITUTION
|
|
5684
|
Univial
|
40 mg/1 mL
|
40 mg/mL
|
|
5685
|
Univial
|
125 mg/2 mL
|
62.5 mg/mL
|
Before mixing, protect from light. Store at 20 to 25°C
(68 to 77°F). [See USP Controlled Room Temperature.]
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©Hospira 2005
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EN-0937
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Printed in USA
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HOSPIRA, INC., LAKE FOREST,
IL 60045 USA
| A-Methapred (Methylprednisolone Sodium Succinate) |
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| A-Methapred (Methylprednisolone Sodium Succinate) |
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Revised: 05/2006HOSPIRA, INC.