A-Methapred

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, (6a, 11ß), and the molecular weight is 496.53.

The structural formula is represented below:

Methylprednisolone 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.

A-Methapred (methylprednisolone sodium succinate) is available in several strengths and packages for intravenous or intramuscular administration.

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 (methylprednisolone sodium succinate) .

Use within 48 hours after mixing.

INDICATIONS

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) sterile powder is indicated for intravenous or intramuscular use in the following conditions:

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
   • Hypercalcemia associated with cancer
   • Nonsuppurative thyroiditis
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
   • Systemic dermatomyositis (polymyositis)
   • Acute rheumatic carditis
4. Dermatologic Diseases
   • Pemphigus
   • Severe erythema multi-forme (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
   • Allergic corneal marginal ulcers
   • Keratitis
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 (IV only; IM 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. Nervous System
    • Acute exacerbations of multiple sclerosis
13. Miscellaneous
    • Tuberculous meningitis with subarachnoid block or impending block when used concurrently with appropriate antituberculous chemotherapy
    • Trichinosis with neurologic or myocardial involvement

      DOSAGE AND ADMINISTRATION

      When high dose therapy is desired, the recommended dose of A-Methapred (methylprednisolone sodium succinate) 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.

      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.

      A-Methapred (methylprednisolone sodium succinate) 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.

      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).

      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.

    • Storage Conditions

      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.]

      Use solution within 48 hours after mixing.

    • SIDE EFFECTS

      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, and 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 (pseudo-tumor 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

      DRUG INTERACTIONS

      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.

    • WARNINGS

      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 corticosteroi