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methylprednisolone sodium succinate injection, solution
SUCCINATE FOR INJECTION, USP)
For Intravenous or Intramuscular Use
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 11β,17,21-Trihydroxy-6α-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.
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.
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:
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.
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.
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.
Fluid and Electrolyte Disturbances
The following additional adverse reactions are related to parenteral corticosteroid therapy:
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.
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
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.
Sterile A-METHAPRED (methylprednisolone sodium succinate for injection, USP) is supplied as follows:
Before mixing, protect from light. Store at 20 to 25°C (68 to 77°F). [See USP Controlled Room Temperature.]
HOSPIRA, INC., LAKE FOREST, IL 60045 USA
Revised: 05/2006 HOSPIRA, INC.
Reproduced with permission of U.S. National Library of Medicine
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