A-Methapred (Methylprednisolone Sodium Succinate) - Summary

A-METHAPRED SUMMARY

A-METHAPRED^®
Methylprednisolone
Sodium Succinate for
Injection, USP

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.

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:

1. 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.

2. 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.

3. 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.

4. 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.

5. 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).

6. 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.

7. Gastrointestinal diseases — To tide the patient over a critical period of disease in:

   a. Ulcerative colitis — (Systemic therapy).

   b. Regional enteritis — (Systemic therapy).

8. 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.

9. 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.

10. Neoplastic diseases — For palliative management of:

    a. Leukemias and lymphomas in adults.

    b. Acute leukemia of childhood.

11. 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.

12. Nervous system:

    a. Acute exacerbations of multiple sclerosis.

13. Miscellaneous:

    a. Tuberculous meningitis with subarachnoid block or impending block when used concurrently with appropriate antituberculous chemotherapy.

    b. Trichinosis with neurologic and myocardial involvement.

NEWS HIGHLIGHTS

Published Studies Related to A-Methapred (Methylprednisolone)

Steroids for early acute respiratory distress syndrome: Critical appraisal of Meduri GU, Golden E, Freire AX, et al: Methylprednisolone infusion in early severe ARDS: Results of a randomized controlled trial. Chest 2007; 131:954-963. [2009.10.13]
OBJECTIVES:: To review the findings and discuss the implications of studies evaluating the use of corticosteroids in early acute respiratory distress syndrome... CONCLUSIONS:: The protocol suggested by Meduri and colleagues presents an attractive therapeutic adjunct, but steroids in early acute respiratory distress syndrome cannot be recommended as standard therapy at this time.

Limb-girdle muscular dystrophy type 2D gene therapy restores alpha-sarcoglycan and associated proteins. [2009.09]
OBJECTIVE: alpha-Sarcoglycan deficiency results in a severe form of muscular dystrophy (limb-girdle muscular dystrophy type 2D [LGMD2D]) without treatment. Gene replacement represents a strategy for correcting the underlying defect. Questions related to this approach were addressed in this clinical trial, particularly the need for immunotherapy and persistence of gene expression... INTERPRETATION: The finding of this gene replacement study in LGMD2D has important implications for muscular dystrophy. Sustained gene expression was seen, but studies over longer time periods without immunotherapy will be required for design of vascular delivery gene therapy trials.

The proinflammatory environment in potential heart and lung donors: prevalence and impact of donor management and hormonal therapy. [2009.08.27]
BACKGROUND: Brain stem death can elicit a potentially manipulable cardiotoxic proinflammatory cytokine response. We investigated the prevalence of this response, the impact of donor management with tri-iodothyronine (T3) and methylprednisolone (MP) administration, and the relationship of biomarkers to organ function and transplant suitability... CONCLUSIONS: There is high prevalence of a proinflammatory environment in the organ donor that is not affected by tri-iodothyronine or MP therapy. High PCT and TNF-alpha levels are associated with donor heart dysfunction.

Is combination rituximab with cyclophosphamide better than rituximab alone in the treatment of lupus nephritis? [2009.08]
OBJECTIVE: To assess if combination rituximab and cyclophosphamide is more effective than rituximab monotherapy as an induction therapy for proliferative lupus nephritis... CONCLUSIONS: Rituximab monotherapy appears to be effective as induction therapy in lupus nephritis. The addition of cyclophosphamide offers no additional improvement in clinical, laboratory and renal histological assessment or the duration of B-cell depletion at 48 weeks. Large-scale studies with longer duration are needed to confirm these findings.

Safety profile and clinical outcomes in a phase I, placebo-controlled study of siplizumab in acute graft-versus-host disease. [2009.07.27]
BACKGROUND: Acute graft-versus-host disease (GVHD) is a major complication of both bone marrow and hematologic stem cell allografts. T cells and natural killer (NK) cells have been linked to the development of GVHD. Modulation of these cells via the CD2 receptor may be a potentially important approach to the management of this disease... CONCLUSION: Siplizumab administered with corticosteroid therapy for grade II or higher acute GVHD treatment exhibited an acceptable safety profile that would support further clinical development.

more studies >>

Clinical Trials Related to A-Methapred (Methylprednisolone)

High-Dose Methylprednisolone and Rituximab in High Risk B-CLL [Recruiting]
Studies have shown that both high-dose Methylprednisolone and Rituximab used as single agents are effective in relapsed and refractory B-CLL. Methylprednisolone acts independently of p53 apoptosis pathway. The combination of both drugs may improve response and outcome in previously treated high-risk B-CLL patients.

Study Objectives

Primary:

To determine the clinical benefit of high-dose Methylprednisolone and Rituximab in previously treated high-risk B-CLL patients in terms of clinical and flowcytometric response rate.

Secondary:

To determine progression free and overall survival. To characterize the safety profile of high-dose Methylprednisolone and Rituximab.

Evaluation of the Efficacy of Topical Ophthalmic Steroids in a Modified Conjunctival Allergen Challenge Model [Active, not recruiting]
The purpose of the study is to determine whether prednisolone acetate 1% ophthalmic suspension is effective in preventing signs and symptoms of allergic conjunctivitis in comparison with prednisolone acetate 0. 12% ophthalmic suspension, loteprednol etabonate 0. 2% ophthalmic suspension and placebo in a modified conjunctival allergen challenge (CAC) model.

Scandinavian Bell's Palsy Study [Completed]
The main objective of this study is to study the effects of prednisolone and valaciclovir, with equal importance, compared to placebo for the treatment of Bell´s palsy. The combination of prednisolone and valaciclovir will also be studied.

A Bioequivalence Study of Tobramycin and Prednisolone Acetate Compared to PredForte [Completed]

Thyroid Treatment Trial [Recruiting]
This project will compare the efficacy and safety of 2 methods of disease modification in the treatment of active moderate and severe thyroid orbitopathy. A prospective, randomized, double-blind, parallel, controlled multidisciplinary clinical trial involving Singapore National Eye Centre, National University Hospital, Changi General Hospital, Tan Tock Seng Hospital and University of British Columbia Orbital Services, Singapore Eye Research Institute, Singapore General Hospital Endocrinology and Radiology Departments and Tan Tock Seng Hospital Rheumatology Department is planned. The SingHealth-SGH High Field MR Research Laboratory will be involved in the MR imaging of the trial patients.

Patients who satisfy the inclusion and exclusion criteria will be asked to participate in this trial. After informed consent (Appendix B) is obtained, each patient will be randomized into one of two treatment arms: 1) Intravenous high-dose pulsed methylprednisolone (1 gram infusion over 1 hour per day with a total of 3 doses over 3 days; 4 cycles at 6 weekly intervals) and oral placebo and 2) Intravenous high-dose pulsed methylprednisolone (same dose) plus oral methotrexate 7. 5 mg per week for 2 weeks, increased to 10 mg per week for another 2 weeks then 12. 5 mg per week for 5 months (total 6 months of methotrexate treatment). Depending on patient response, the dose can be further increased by 2. 5mg per week every 4 weeks to a maximum of 20 mg per week. A strict management protocol will be observed for each recruited patient. Patients who develop adverse side effects or need for surgical intervention will receive appropriate treatment (i. e. treatment will deviate from the protocol but will continue to be monitored). Patients who refuse treatment will be observed clinically and with imaging as a natural control group until such time as intervention is accepted.

The patients will have a baseline assessment followed by regular visits to assess treatment response and adverse effects. Observations will include the use of an inflammatory index, motility measurements including quantitative ductions, exophthalmometry readings, palpebral aperture readings and indices of optic nerve function. With regards to the imaging, the patients will be assessed with an initial quantitative CT scan and 3-Tesla MRI scan prior to treatment. After treatment is started, patients will also undergo repeat MRI scan at 24 weeks and 72 weeks to assess quantitative changes with treatment using the Muscle Diameter Index (MDI) and Pixel Value Ratio (PVR) for the inferior rectus, superior rectus, the medial rectus, lateral rectus and orbital fat (Appendix E). Serum and urine will be obtained at the same time intervals as the MRI scan to assess levels of thyroid hormones, thyroid antibodies and urinary glycosaminoglycans (GAGs). Free T4, free T3 and TSH will be recorded to monitor control of hyperthyroidism. Thyroid antibodies measured will include thyroid stimulating immunoglobulin (TSI), thyrotropin-binding inhibition antibody (TB II), thyroid peroxidase antibodies and thyroglobulin antibody. Other tests including the full blood count, urea and electrolytes will be run prior to each dose of steroid treatment and during follow-up to monitor for adverse effects.

The results of the assessments will be analyzed for significant differences in treatment response between the 2 groups. The indices of interest will include the percentage of patients in each group who demonstrate a decrease in the inflammatory index of at least 2 points and the time taken for 50% of patients to show such a decrease. Other parameters that reflect the visual function and motility will be compared at different points in time after starting treatment to observe response and sustainability of response. From the serial MRI scans, quantitative analysis of orbital tissues will be done to identify changes with treatment. Antibody and GAG levels will be analyzed to detect any change with treatment. The types and frequency of adverse side effects in the 2 groups will also be assessed.

80 normal subjects will be recruited for MRI scan of the orbits and brain to obtain normative values for the MDI and PVR for the Asian population (Appendix E). This will include 20 subjects from each of 4 decades (21-30 years, 31-40 years, 41-50 years, 51-60 years).

The normative data will also be used to create a virtual orbital atlas. This aspect of the study will be performed in collaboration with the Labs for Information Technology (A-Star).

more trials >>