A-METHAPRED®Methylprednisolone Sodium Succinate for Injection,
methylprednisolone sodium succinate injection, powder, lyophilized, for solution Hospira, Inc.
A-METHAPRED® Methylprednisolone Sodium Succinate for Injection,
For Intravenous or Intramuscular Administration
A-Methapred (methylprednisolone sodium succinate
for injection, USP) sterile powder contains methylprednisolone sodium
succinate as the active ingredient. Methylprednisolone sodium succinate,
USP, occurs as a white, or nearly white, odorless hygroscopic, amorphous
solid. It is very soluble in water and in alcohol; it is insoluble
in chloroform and is very slightly soluble in acetone.
The chemical name for methylprednisolone sodium
succinate is pregna-1,4-diene-3,20-dione,21-(3-carboxy-1-oxo-propoxy)-11,17-dihydroxy-6-methyl-monosodium
salt, (6α, 11β), and the molecular weight is 496.53.
The structural formula is represented below:
sodium succinate is so extremely soluble in water that it may be administered
in a small volume of diluent and is especially well suited for intravenous
use in situations in which high blood levels of methylprednisolone
are required rapidly.
is available in several strengths and packages for intravenous or
40 mg Single-Dose Vial − Each mL
(when mixed) contains methylprednisolone sodium succinate equivalent
to 40 mg methylprednisolone; also 1.6 mg monobasic sodium phosphate
anhydrous; 17.46 mg dibasic sodium phosphate anhydrous; 25 mg lactose
anhydrous; 8.8 mg benzyl alcohol added as preservative.
125 mg Single-Dose Vial − Each 2 mL (when mixed) contains methylprednisolone sodium
succinate equivalent to 125 mg methylprednisolone; also 1.6 mg monobasic
sodium phosphate anhydrous; 17.4 mg dibasic sodium phosphate anhydrous;
17.6 mg benzyl alcohol added as preservative.
When necessary, the pH of each formula was adjusted
with sodium hydroxide so that the pH of the reconstituted solution
is within the USP specified range of 7 to 8 and the tonicities are,
for the 40 mg per mL solution, 0.50 osmolar; for the 125 mg per 2
mL, 0.40 osmolar; (Isotonic saline = 0.28 osmolar).
IMPORTANT − Use only Bacteriostatic
Water For Injection with Benzyl Alcohol when reconstituting A-Methapred.
Use within 48 hours after mixing.
Methylprednisolone is a potent anti-inflammatory
steroid with 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, the two compounds
are equivalent in biologic activity. The relative potency of A-Methapred
sterile powder 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 sterile
powder is indicated for intravenous or intramuscular use in the following
• 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)
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
• Shock unresponsive
to conventional therapy if adrenocortical insufficiency exists or
• Congenital adrenal
• Hypercalcemia associated
• Nonsuppurative thyroiditis
As adjunctive therapy for short-term
administration (to tide the patient over an acute episode or exacerbation)
• Post-traumatic osteoarthritis
• Synovitis of osteoarthritis
• Rheumatoid arthritis, including juvenile
rheumatoid arthritis (selected cases may require low-dose maintenance
• Acute and subacute bursitis
• Acute nonspecific tenosynovitis
• Acute gouty arthritis
During an exacerbation or as maintenance
therapy in selected cases of:
Systemic lupus erythematosus
Acute rheumatic carditis
• Severe erythema multi-forme (Stevens-Johnson
• Exfoliative dermatitis
• Bullous dermatitis herpetiformis
• Severe seborrheic dermatitis
• Severe psoriasis
Control of severe or incapacitating allergic
conditions intractable to adequate trials of conventional treatment
• Bronchial asthma
• Contact dermatitis
• Atopic dermatitis
• Seasonal or perennial
• Drug hypersensitivity
• Urticarial transfusion
• Acute noninfectious
laryngeal edema (epinephrine is the drug of first choice)
Severe acute and chronic allergic and
inflammatory processes involving the eye, such as:
• Herpes zoster ophthalmicus
• Iritis, iridocyclitis
• Diffuse posterior
uveitis and choroiditis
• Sympathetic ophthalmia
• Anterior segment inflammation
• Allergic conjunctivitis
• Allergic corneal marginal ulcers
To tide the patient over a critical period
of the disease in:
colitis (systemic therapy)
enteritis (systemic therapy)
• Symptomatic sarcoidosis
Fulminating or disseminated pulmonary tuberculosis when used concurrently
with appropriate antituberculous chemotherapy
• Loeffler’s syndrome not manageable by other
• Aspiration pneumonitis
• Acquired (autoimmune) hemolytic
• Idiopathic thrombocytopenic
purpura in adults (IV only; IM administration is contraindicated)
• Secondary thrombocytopenia in adults
• Erythroblastopenia (RBC anemia)
• Congenital (erythroid) hypoplastic anemia
For palliative management of:
• Leukemias and lymphomas in adults
• Acute leukemia of childhood
• To induce diuresis or remission
of proteinuria in the nephrotic syndrome, without uremia, of the idiopathic
type or that due to lupus erythematosus
• Acute exacerbations of multiple
• Tuberculous meningitis with
subarachnoid block or impending block when used concurrently with
appropriate antituberculous chemotherapy
• Trichinosis with neurologic or myocardial involvement
The use of A-Methapred sterile powder is contraindicated
in premature infants because the reconstitution diluent contains benzyl
alcohol. Benzyl alcohol has been reported to be associated with a
fatal “Gasping Syndrome” in premature infants. A-Methapred
sterile powder is also contraindicated in systemic fungal infections
and patients with known hypersensitivity to the product and its constituents.
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.
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
A study has failed to
establish the efficacy of Methylprednisolone Sodium Succinate for
Injection, USP in the treatment of sepsis syndrome and septic shock.
The study also suggests that treatment of these conditions with Methylprednisolone
Sodium Succinate for Injection, USP may increase the risk of mortality
in certain patients (ie, patients with elevated serum creatinine levels
or patients who develop secondary infections after Methylprednisolone
Sodium Succinate for Injection, USP.
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 child-bearing 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.
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.
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
The use of Methylprednisolone Sodium
Succinate for Injection, USP sterile powder 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 (eg,
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.
reports of cardiac arrhythmias and/or circulatory collapse and/or
cardiac arrest following the rapid administration of large IV doses
of Methylprednisolone Sodium Succinate for Injection, USP (greater
than 0.5 gram 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 infusion.
Persons who are on drugs which suppress the immune system are more
susceptible to infections than healthy individuals. Chicken pox 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 chicken pox, 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 chicken pox develops, treatment with antiviral agents may be considered.
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
There is an enhanced
effect of corticosteroids on patients with hypothyroidism and in those
should be used cautiously in patients with ocular herpes simplex because
of possible corneal perforation.
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.
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.
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.
Growth and development of infants and children on prolonged corticosteroid
therapy should be carefully observed.
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.)
Since complications of treatment
with glucocorticoids are dependent on the size of the dose and 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.
The pharmacokinetic interactions listed below are
potentially clinically important. Mutual inhibition of metabolism
occurs with concurrent use of cyclosporin and methylprednisolone;
therefore, it is possible that adverse events associated with the
individual use of either drug may be more apt to occur. Convulsions
have been reported with concurrent use of methylprednisolone and cyclosporin.
Information for the Patient
Persons who are on immunosuppressant doses of corticosteroids
should be warned to avoid exposure to chicken pox or measles. Patients
should also be advised that if they are exposed, medical advice should
be sought without delay.
Steroid myopathy, Loss of muscle mass, Severe arthralgia, Vertebral
compression fractures, Aseptic necrosis of femoral and humeral heads,
Pathologic fracture of long bones, Osteoporosis
Peptic ulcer with possible perforation and hemorrhage,
Pancreatitis, Abdominal distention, and Ulcerative esophagitis
Impaired wound healing, Thin fragile skin, Petechiae and
ecchymoses, Facial erythema, Increased sweating, May suppress reactions
to skin tests
Increased intracranial pressure with papilledema
(pseudo-tumor cerebri) usually after treatment, Convulsions, Vertigo,
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
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 A-Methapred sterile powder 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.
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
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 5% dextrose in water, isotonic saline
solution or 5% dextrose in isotonic saline solution.
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).
Directions for Reconstitution
Remove protective cap.
Cleanse stopper with suitable germicide.
Aseptically add 1 mL Bacteriostatic Water for Injection,
USP (with benzyl alcohol) for the 40 mg vial or 2 mL Bacteriostatic
Water for Injection, USP (with benzyl alcohol) for the 125 mg vial.
Agitate to effect solution.
Invert vial. Insert needle through target area of
stopper until tip is just visible. Withdraw dose.
Protect from light.
Store unreconstituted product at 20 to 25°C (68
to 77°F). [See USP Controlled Room Temperature.]
Store solution at 20 to 25°C (68 to 77°F).
[See USP Controlled Room Temperature.]
solution within 48 hours after mixing.
A-Methapred sterile powder is available in the following
Revised: April, 2008
Printed in USA
Hospira, Inc., Lake Forest, IL 60045 USA
methylprednisolone sodium succinate injection, powder, lyophilized, for solution