Romamed

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

Romamed powder and solvent for injection/infusion is indicated to treat any condition in which rapid and intense corticosteroid effect is required such as:

1. Dermatological disease

Severe erythema multiforme (Stevens Johnson syndrome)

2. Allergic states

Bronchial asthma

Severe seasonal and perennial allergic rhinitis

Angioneurotic oedema

Anaphylaxis

3. Gastro intestinal diseases

Ulcerative colitis

Crohn's disease

4. Respiratory diseases

Aspiration of gastric contents

Fulminating or disseminated tuberculosis (with appropriate antituberculous chemotherapy)

5. Neurological disorders

Cerebral oedema secondary to cerebral tumour

Acute exacerbations of multiple sclerosis superimposed on a relapsing/remitting background.

6. Miscellaneous

T.B. meningitis (with appropriate antituberculous chemotherapy)

Transplantation

Romamed (methylprednisolone) Tablets are indicated in the following conditions:

1.  Endocrine Disorders

Primary or secondary adrenocortical insufficiency (hydrocortisone or cortisone is the first choice; synthetic analogs may be used in conjunction with mineralocorticoids where applicable; in infancy mineralocorticoid supplementation is of particular importance).
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:
Rheumatoid arthritis, including juvenile rheumatoid arthritis (selected cases may require low-dose maintenance therapy)
Ankylosing spondylitis
Acute and subacute bursitis
Synovitis of osteoarthritis
Acute nonspecific tenosynovitis
Post-traumatic osteoarthritis
Psoriatic arthritis
Epicondylitis
Acute gouty arthritis

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

Bullous dermatitis herpetiformis
Severe erythema multiforme
(Stevens-Johnson syndrome)
Severe seborrheic dermatitis
Exfoliative dermatitis
Mycosis fungoides
Pemphigus
Severe psoriasis

5. Allergic States

Control of severe or incapacitating allergic conditions intractable to adequate trials of conventional treatment:
Seasonal or perennial allergic rhinitis
Drug hypersensitivity reactions
Serum sickness
Contact dermatitis
Bronchial asthma
Atopic dermatitis

6. Ophthalmic Diseases

Severe acute and chronic allergic and inflammatory processes involving the eye and its adnexa such as: Allergic corneal marginal ulcers
Herpes zoster ophthalmicus
Anterior segment inflammation
Diffuse posterior uveitis and choroiditis
Sympathetic ophthalmia
Keratitis
Optic neuritis
Allergic conjunctivitis
Chorioretinitis
Iritis and iridocyclitis

7. Respiratory Diseases

Symptomatic sarcoidosis
Berylliosis
Loeffler's syndrome not manageable by other means
Fulminating or disseminated pulmonary tuberculosis when used concurrently with appropriate antituberculous chemotherapy
Aspiration pneumonitis

8. Hematologic Disorders

Idiopathic thrombocytopenic purpura in adults
Secondary thrombocytopenia in adults
Acquired (autoimmune) hemolytic anemia
Erythroblastopenia (RBC anemia)
Congenital (erythroid) hypoplastic anemia

9.  Neoplastic Diseases

For palliative management of:
Leukemias and lymphomas in adults
Acute leukemia of childhood

10. Edematous States

To induce a diuresis or remission of proteinuria in the nephrotic syndrome, without uremia, of the idiopathic type or that due to lupus erythematosus.

11. Gastrointestinal Diseases

To tide the patient over a critical period of the disease in:
Ulcerative colitis
Regional enteritis

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.

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, Romamed (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

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

1. Remove protective cap.
2. Cleanse stopper with suitable germicide.
3. 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.
4. Agitate to effect solution.
5. 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).

Store solution at 20 to 25°C (68 to 77°F).

Use solution within 48 hours after mixing.

Posology

Romamed powder for injection/infusion may be administered intravenously or intramuscularly, the preferred method for emergency use being intravenous injection given over a suitable time interval. When administering Romamed sodium succinate in high doses intravenously it should be given over a period of at least 30 minutes. Doses up to 250 mg should be given intravenously over a period of at least five minutes.

For intravenous infusion the initially prepared solution may be diluted with 5% dextrose in water, isotonic saline solution, or 5% dextrose in isotonic saline solution. To avoid compatibility problems with other drugs Romamed powder for injection/infusion should be administered separately, only in the solutions mentioned. Undesirable effects may be minimised by using the lowest effective dose for the minimum period (see Other special warnings and precautions).

Parenteral drug products should wherever possible be visually inspected for particulate matter and discoloration prior to administration.

Adults: Dosage should be varied according to the severity of the condition, initial dosage will vary from 10 to 500 mg. In the treatment of graft rejection reactions following transplantation, a dose of up to 1 gram/day may be required. Although doses and protocols have varied in studies using Romamed sodium succinate in the treatment of graft rejection reactions, the published literature supports the use of doses of this level, with 500 mg to 1 g most commonly used for acute rejection.

Treatment at these doses should be limited to a 48 - 72 hour period until the patient's condition has stabilised, as prolonged high dose corticosteroid therapy can cause serious corticosteroid induced side effects (see Undesirable effects and Special warnings and special precautions for use).

Children: In the treatment of high dose indications, such as haematological, rheumatic, renal and dermatological conditions, a dosage of 30 mg/kg/day to a maximum of 1 g/day is recommended.

This dosage may be repeated for three pulses either daily or on alternate days. In the treatment of graft rejection reactions following transplantation, a dosage of 10 to 20 mg/kg/day for up to 3 days, to a maximum of 1 g/day, is recommended. In the treatment of status asthmaticus, a dosage of 1 to 4 mg/kg/day for 1- 3 days is recommended.

Elderly patients: Romamed sodium succinate powder for injection/infusion is primarily used in acute short term conditions. There is no information to suggest that a change in dosage is warranted in the elderly. However, treatment of elderly patients should be planned bearing in mind the more serious consequences of the common side-effects of corticosteroids in old age and close clinical supervision is required (see Special warnings and special precautions for use).

Detailed recommendations for adult dosage are as follows:

In anaphylactic reactions adrenaline or noradrenaline should be administered first for an immediate haemodynamic effect, followed by intravenous injection of Romamed sodium succinate with other accepted procedures. There is evidence that corticosteroids through their prolonged haemodynamic effect are of value in preventing recurrent attacks of acute anaphylactic reactions.

In sensitivity reactions Romamed sodium succinate is capable of providing relief within one half to two hours.

In patients with status asthmaticus Romamed sodium succinate may be given at a dose of 40 mg intravenously, repeated as dictated by patient response. In some asthmatic patients it may be advantageous to administer by slow intravenous drip over a period of hours.

In graft rejection reactions following transplantation doses of up to 1 g per day have been used to suppress rejection crises, with doses of 500 mg to 1 g most commonly used for acute rejection. Treatment should be continued only until the patient's condition has stabilised; usually not beyond 48 - 72 hours.

In cerebral oedema corticosteroids are used to reduce or prevent the cerebral oedema associated with brain tumours (primary or metastatic).

In patients with oedema due to tumour, tapering the dose of corticosteroid appears to be important in order to avoid a rebound increase in intracranial pressure. If brain swelling does occur as the dose is reduced (intracranial bleeding having been ruled out), restart larger and more frequent doses parenterally. Patients with certain malignancies may need to remain on oral corticosteroid therapy for months or even life. Similar or higher doses may be helpful to control oedema during radiation therapy.

The following are suggested dosage schedules for oedemas due to brain tumour.

Aim to discontinue therapy after a total of 10 days.

In the treatment of acute exacerbations of multiple sclerosis in adults, the recommended dose is 1000 mg daily for 3 days. Romamed powder for injection/infusion should be given as an intravenous infusion over at least 30 minutes.

In other indications, initial dosage will vary from 10 to 500 mg depending on the clinical problem being treated. Larger doses may be required for short term management of severe, acute conditions. The initial dose, up to 250 mg, should be given intravenously over a period of at least 5 minutes, doses exceeding 250 mg should be given intravenously over a period of at least 30 minutes. Subsequent doses may be given intravenously or intramuscularly at intervals dictated by the patient's response and clinical condition. Corticosteroid therapy is an adjunct to, and not replacement for, conventional therapy.

Method of administration

To be administered intravenously or intramuscularly.

The initial dosage of Romamed Tablets may vary from 4 mg to 48 mg of methylprednisolone per day depending on the specific disease entity being treated. In situations of less severity lower doses will generally suffice while in selected patients higher initial doses may be required. The initial dosage should be maintained or adjusted until a satisfactory response is noted. If after a reasonable period of time there is a lack of satisfactory clinical response, Romamed (methylprednisolone) should be discontinued and the patient transferred to other appropriate therapy.

IT SHOULD BE EMPHASIZED THAT DOSAGE REQUIREMENTS ARE VARIABLE AND MUST BE INDIVIDUALIZED ON THE BASIS OF THE DISEASE UNDER TREATMENT AND THE RESPONSE OF THE PATIENT. After a favorable response is noted, the proper maintenance dosage should be determined by decreasing the initial drug dosage in small decrements at appropriate time intervals until the lowest dosage which will maintain an adequate clinical response is reached. It should be kept in mind that constant monitoring is needed in regard to drug dosage. Included in the situations which may make dosage adjustments necessary are changes in clinical status secondary to remissions or exacerbations in the disease process, the patient's individual drug responsiveness, and the effect of patient exposure to stressful situations not directly related to the disease entity under treatment; in this latter situation it may be necessary to increase the dosage of Romamed (methylprednisolone) for a period of time consistent with the patient's condition. If after long-term therapy the drug is to be stopped, it is recommended that it be withdrawn gradually rather than abruptly.

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).

ADT® (Alternate Day Therapy)

Alternate day therapy is a corticosteroid dosing regimen in which twice the usual daily dose of corticoid is administered every other morning. The purpose of this mode of therapy is to provide the patient requiring long-term pharmacologic dose treatment with the beneficial effects of corticoids while minimizing certain undesirable effects, including pituitary-adrenal suppression, the Cushingoid state, corticoid withdrawal symptoms, and growth suppression in children.

The rationale for this treatment schedule is based on two major premises: (a) the anti-inflammatory or therapeutic effect of corticoids persists longer than their physical presence and metabolic effects and (b) administration of the corticosteroid every other morning allows for reestablishment of more nearly normal hypothalamic-pituitary-adrenal (HPA) activity on the off-steroid day.

A brief review of the HPA physiology may be helpful in understanding this rationale. Acting primarily through the hypothalamus a fall in free cortisol stimulates the pituitary gland to produce increasing amounts of corticotropin (ACTH) while a rise in free cortisol inhibits ACTH secretion. Normally the HPA system is characterized by diurnal (circadian) rhythm. Serum levels of ACTH rise from a low point about 10 pm to a peak level about 6 am. Increasing levels of ACTH stimulate adrenal cortical activity resulting in a rise in plasma cortisol with maximal levels occurring between 2 am and 8 am. This rise in cortisol dampens ACTH production and in turn adrenal cortical activity. There is a gradual fall in plasma corticoids during the day with lowest levels occurring about midnight.

The diurnal rhythm of the HPA axis is lost in Cushing's disease, a syndrome of adrenal cortical hyperfunction characterized by obesity with centripetal fat distribution, thinning of the skin with easy bruisability, muscle wasting with weakness, hypertension, latent diabetes, osteoporosis, electrolyte imbalance, etc. The same clinical findings of hyperadrenocorticism may be noted during long-term pharmacologic dose corticoid therapy administered in conventional daily divided doses. It would appear, then, that a disturbance in the diurnal cycle with maintenance of elevated corticoid values during the night may play a significant role in the development of undesirable corticoid effects. Escape from these constantly elevated plasma levels for even short periods of time may be instrumental in protecting against undesirable pharmacologic effects.

During conventional pharmacologic dose corticosteroid therapy, ACTH production is inhibited with subsequent suppression of cortisol production by the adrenal cortex. Recovery time for normal HPA activity is variable depending upon the dose and duration of treatment. During this time the patient is vulnerable to any stressful situation. Although it has been shown that there is considerably less adrenal suppression following a single morning dose of prednisolone (10 mg) as opposed to a quarter of that dose administered every six hours, there is evidence that some suppressive effect on adrenal activity may be carried over into the following day when pharmacologic doses are used. Further, it has been shown that a single dose of certain corticosteroids will produce adrenal cortical suppression for two or more days. Other corticoids, including methylprednisolone, hydrocortisone, prednisone, and prednisolone, are considered to be short acting (producing adrenal cortical suppression for 1¼ to 1½ days following a single dose) and thus are recommended for alternate day therapy.

The following should be kept in mind when considering alternate day therapy:

1. Basic principles and indications for corticosteroid therapy should apply. The benefits of ADT should not encourage the indiscriminate use of steroids.
2. ADT is a therapeutic technique primarily designed for patients in whom long-term pharmacologic corticoid therapy is anticipated.
3. In less severe disease processes in which corticoid therapy is indicated, it may be possible to initiate treatment with ADT. More severe disease states usually will require daily divided high dose therapy for initial control of the disease process. The initial suppressive dose level should be continued until satisfactory clinical response is obtained, usually four to ten days in the case of many allergic and collagen diseases. It is important to keep the period of initial suppressive dose as brief as possible particularly when subsequent use of alternate day therapy is intended.
   Once control has been established, two courses are available: (a) change to ADT and then gradually reduce the amount of corticoid given every other day or (b) following control of the disease process reduce the daily dose of corticoid to the lowest effective level as rapidly as possible and then change over to an alternate day schedule. Theoretically, course (a) may be preferable.
4. Because of the advantages of ADT, it may be desirable to try patients on this form of therapy who have been on daily corticoids for long periods of time (eg, patients with rheumatoid arthritis). Since these patients may already have a suppressed HPA axis, establishing them on ADT may be difficult and not always successful. However, it is recommended that regular attempts be made to change them over. It may be helpful to triple or even quadruple the daily maintenance dose and administer this every other day rather than just doubling the daily dose if difficulty is encountered. Once the patient is again controlled, an attempt should be made to reduce this dose to a minimum.
5. As indicated above, certain corticosteroids, because of their prolonged suppressive effect on adrenal activity, are not recommended for alternate day therapy (eg, dexamethasone and betamethasone).
6. The maximal activity of the adrenal cortex is between 2 am and 8 am, and it is minimal between 4 pm and midnight. Exogenous corticosteroids suppress adrenocortical activity the least, when given at the time of maximal activity (am).
7. In using ADT it is important, as in all therapeutic situations to individualize and tailor the therapy to each patient. Complete control of symptoms will not be possible in all patients. An explanation of the benefits of ADT will help the patient to understand and tolerate the possible flare-up in symptoms which may occur in the latter part of the off-steroid day. Other symptomatic therapy may be added or increased at this time if needed.
8. In the event of an acute flare-up of the disease process, it may be necessary to return to a full suppressive daily divided corticoid dose for control. Once control is again established alternate day therapy may be reinstituted.
9. Although many of the undesirable features of corticosteroid therapy can be minimized by ADT, as in any therapeutic situation, the physician must carefully weigh the benefit-risk ratio for each patient in whom corticoid therapy is being considered.

When high dose therapy is desired, the recommended dose of Romamed (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.

Romamed (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

1. Remove protective cap.
2. Cleanse stopper with suitable germicide.
3. 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.
4. Agitate to effect solution.
5. 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).

Store solution at 20 to 25°C (68 to 77°F).

Use solution within 48 hours after mixing.

The use of A-Methapred (methylprednisolone sodium succinate) 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 (methylprednisolone sodium succinate) sterile powder is also contraindicated in systemic fungal infections and patients with known hypersensitivity to the product and its constituents.

Romamed powder for injection/infusion is contraindicated:

- in patients who have systemic fungal infections unless specific anti-infective therapy is employed and in cerebral oedema in malaria.

- in patients with known hypersensitivity to Romamed or any component of the formulation.

- for use by the intrathecal route of administration.

Administration of live or live, attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of corticosteroids.

Systemic fungal infections and known hypersensitivity to components.

The use of Romamed (methylprednisolone sodium succinate) 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. Romamed (methylprednisolone sodium succinate) sterile powder is also contraindicated in systemic fungal infections and patients with known hypersensitivity to the product and its constituents.