(British Approved Name, rINN)
Pharmacopoeias. In Europe, Japan, and US.
European Pharmacopoeia, 6th ed. (Methylprednisolone). A white or almost white, crystalline powder. It shows polymorphism. Practically insoluble in water sparingly soluble in alcohol slightly soluble in acetone and in dichloromethane. Protect from light.
The United States Pharmacopeia 31, 2008 (Methylprednisolone). A white to practically white, odourless, crystalline powder. Practically insoluble in water soluble 1 in 100 of alcohol, and in 1 in 800 of chloroform and of ether slightly soluble in acetone sparingly soluble in dioxan and in methyl alcohol. Store in airtight containers. Protect from light.
(British Approved Name Modified, rINNM)
Pharmacopoeias. In Europe and US.
European Pharmacopoeia, 6th ed. (Methylprednisolone Acetate). A white or almost white, crystalline powder. Practically insoluble in water sparingly soluble in alcohol and in acetone. Protect from light.
The United States Pharmacopeia 31, 2008 (Methylprednisolone Acetate). A white or practically white, odourless, crystalline powder. Soluble 1 in 1500 of water, 1 in 400 of alcohol, 1 in 250 of chloroform, and 1 in 1500 of ether sparingly soluble in acetone and in methyl alcohol soluble in dioxan. Store in airtight containers at a temperature of 25°, excursions permitted between 15° and 30°. Protect from light.
Methylprednisolone Hydrogen Succinate
(British Approved Name Modified, rINNM)
Pharmacopoeias. In Europe, Japan, and US.
European Pharmacopoeia, 6th ed. (Methylprednisolone Hydrogen Succinate). A white or almost white, hygroscopic powder. Practically insoluble in water slightly soluble in dehydrated alcohol and in acetone dissolves in dilute solutions of alkali hydroxides. Store in airtight containers. Protect from light.
The United States Pharmacopeia 31, 2008 (Methylprednisolone Hemisuccinate). A white or nearly white, odourless or nearly odourless, hygroscopic solid. Very slightly soluble in water freely soluble in alcohol soluble in acetone. Store in airtight containers.
Methylprednisolone Sodium Succinate
(British Approved Name Modified, rINNM)
Pharmacopoeias. In US.
The United States Pharmacopeia 31, 2008 (Methylprednisolone Sodium Succinate). A white or nearly white, odourless, hygroscopic, amorphous solid. Soluble 1 in 1.5 of water and 1 in 12 of alcohol very slightly soluble in acetone insoluble in chloroform and in ether. Store in airtight containers. Protect from light.
Methylprednisolone sodium succinate injection (Solu-Medrol USA) was considered to be stable for 7 days when diluted in water for inj ection and stored in glass vials at 4°. When stored under similar conditions at 22°, it was considered to be stable for 24 hours. The manufacturers state that the prepared solution should be stored at 20 to 25° and used within 48 hours of mixing.
Adverse Effects, Treatment, Withdrawal, and Precautions
As for corticosteroids in general. Rapid intravenous injection of large doses has been associated with cardiovascular collapse. Methylprednisolone may be slightly less likely than prednisolone to cause sodium and water retention. When applied topically, particularly to large areas, when the skin is broken, or under occlusive dressings, corticosteroids may be absorbed in sufficient amounts to cause systemic effects.
References to various adverse effects associated with intravenous methylprednisolone in high-dose pulse therapy and to adverse effects after intra-articular and intranasal injection. Epidural dosage (or more particularly inadvertent intrathecal dosage during attempted epidural placement) may be associated with serious adverse effects including arachnoiditis and aseptic meningitis, although the degree of risk is uncertain.
The interactions of corticosteroids in general are described.
For a brief outline of the pharmacokinetics of corticosteroids.
Methylprednisolone is fairly rapidly distributed after oral doses, with a plasma half-life of 3.5 hours or more. The tissue half-life is reported to range from 18 to 36 hours.
Methylprednisolone acetate is absorbed from joints over a week but is more slowly absorbed following deep intramuscular injection. The sodium succinate ester is rapidly absorbed after intramuscular doses, with peak plasma concentrations obtained in 2 hours. Methylprednisolone crosses the placenta.
Uses and Administration
Methylprednisolone is a corticosteroid with mainly glucocorticoid activity 4mg of methylprednisolone is equivalent in anti-inflammatory activity to about 5 mg of prednisolone.
It is used, either in the form of the free alcohol or in one of the esterified forms, in the treatment of conditions for which cortico steroid therapy is indicated except adrenocortical-deficiency states, for which hydrocortisone with supplementary fludrocortisone is preferred.
The dose is usually expressed in terms of the base, and the following are each equivalent to about 40 mg of methylprednisolone:
- methylprednisolone acetate 44 mg
- methylprednisolone hydrogen succinate 51 mg
- methylprednisolone sodium succinate 53 mg When given orally, methylprednisolone usually has an initial dosage range of 4 to 48 mg daily but higher initial doses of up to 100 mg or more daily may be used in acute severe disease.
For parenteral use in intensive or emergency therapy, methylprednisolone sodium succinate may be given by intramuscular or intravenous injection or by intravenous infusion. The intravenous route is preferred for its more rapid effect in emergency therapy. The usual initial intramuscular or intravenous dose ranges from the equivalent of 10 to 500 mg of methylprednisolone daily. Large intravenous doses (over 250 mg) should normally be given slowly over at least 30 minutes doses up to 250 mg should be given over at least 5 minutes. High doses should generally not be given for prolonged periods emergency treatment should only be used until the patient is stabilised.
High doses given intermittently for a limited period have sometimes been known as ‘pulse therapy’ (see Administration, below) and in graft rejection (see Organ and Tissue Transplantation) up to 1 g has been given daily for up to 3 days. In intensive therapy of acute spinal cord injury initial doses of the equivalent of up to 30mg/kg of methylprednisolone have been given by bolus intravenous injection over 15 minutes and followed, after a 45-minute pause, by intravenous infusion of 5.4 mg/kg per hour over 24 hours or longer. For slow intravenous infusion methylprednisolone sodium succinate is dissolved in an appropriate volume of glucose 5% or sodium chloride 0.9% or sodium chloride 0.9% and glucose 5%.
Parenteral doses in children have varied considerably, depending on the condition: a range of 1 to 30 mg/kg of methylprednisolone daily has been given by the intravenous or intramuscular routes. A total dose of 1 g daily should not normally be exceeded. Methylprednisolone acetate may be given by intramuscular injection for a prolonged systemic effect, the dose varying from 40 mg every 2 weeks to 120 mg weekly. For intra-articular injection and for injection into soft tissues methylprednisolone acetate as an aqueous suspension is used. The dose by intra-articular injection varies from 4 to 80 mg according to the size of the affected joint. The acetate may also be given by intra-lesional injection in doses of 20 to 60 mg.
For use in the treatment of various skin disorders methylprednisolone acetate may be applied topically, usually in concentrations of 0.25%. The aceponate, which may exhibit modified topical activity, has also been applied as a 0.1% cream, lotion, or ointment. For recommendations concerning the correct use of corticosteroids on the skin, and a rough guide to the clinical potencies of topical corticosteroids, see p.1497. Other esters of methylprednisolone that have occasionally been used include the cipionate and the suleptanate.
For short-term intensive corticosteroid therapy or in certain emergency situations a technique known as ‘pulse therapy’ has been used. Methylprednisolone has often been used in this manner. Typically, high doses of about 1 g intravenously have been given, daily or on alternate days or weekly, for a limited number of doses the most common regimen appears to be 1 g daily for 3 days.
Methylprednisolone is one of the corticosteroids that have been used in the management of haemangioma and the Kasabach-Merritt syndrome. There are also reports of benefit from very high-dose therapy in a few patients with refractory primary acquired pure red cell aplasia, or aplasia due to Blackfan-Diamond anaemia.
Idiopathic thrombocytopenic purpura.
High-dose intravenous methylprednisolone may be used as part of the emergency management of acute idiopathic thrombocytopenic purpura, for example when major acute bleeding or intracranial haemorrhage supervene. There is some evidence that methylprednisolone is less effective than normal immunoglobulins. Methylprednisolone has also been used by mouth or intravenously in the management of the chronic form, although prednisolone or prednisone are more frequently used for oral therapy and good controlled trials are scanty.
Methylprednisolone given in intravenous pulses has been reported to be effective in the treatment of rheumatoid arthritis including juvenile idiopathic arthritis. Some studies have shown this treatment to be of greatest benefit when given with a disease-modifying antirheumatic drug (DMARD), although others showed the addition of methylprednisolone to existing therapy to have no extra benefit. A comparatively low dose of 100 mg was found to be as effective as 1000 mg in one study. Monthly doses of methylprednisolone by deep intramuscular injection were also an effective adjunct to gold therapy.
A preliminary study in children has found intravenous pulses of methylprednisolone 30 mg/kg to be effective treatment for systemic flares of juvenile idiopathic arthritis.
Systemic lupus erythematosus.
Methylprednisolone has been widely used to treat disease flares or severe manifestations of SLE.
British Pharmacopoeia 2008: Methylprednisolone Acetate Injection Methylprednisolone Tablet
The United States Pharmacopeia 31, 2008: Methylprednisolone Acetate Cream Methylprednisolone Acetate Injectable Suspension Methylprednisolone Sodium Succinate for Injection Methylprednisolone Tablets NeomycinSulfateand Methylprednisolone Acetate Cream.
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Poland: Advantan Depo-Medrol Medrol Metypred Solu-Medrol
Portugal: Advantan Depo-Medrol Medrol Metilpren Solu-Medrol
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Spain: Adventan Depo Moderinf Lexxema Solu-Moderin Urbason
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USA: A-Methapred depMedalone Depo-Medrol Depopred Medrol Solu-Medrol
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Austria: Depo-Medrol mit Lidocain
Belgium: Depo-Medrol + Lidocaine
Canada: Depo-Medrol with Lidocaine Medrol Acne Lotion Neo-Medrol Acne Neo-Medrol Veriderm
Finland: Depo-Medrol cum Lidocain Neo-Medrol comp Solomet c bupivacain hydrochlorid
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Ireland: Depo-Medrone with Lidocaine
Israel: Depo-Medrol with Lidocaine Neo-Medrol
Italy: Depo-Medrol + Lidocaina Medrol Lozione Antiacne- Neo-Medrol Veriderm
The Netherlands: Depo-Medrol + Lidocaine
Norway: Depo-Medrol cum Lidocain
New Zealand: Depo-Medrol with Lidocaine
Poland: Depo-Medrol z Lidokaina
Portugal: Depo-Medrol com Lidocaina
South Africa: Depo-Medrol with Lidocaine Neo-Medrol
Spain: Moderin Acnef
Sweden: Depo-Medrol cum Lidocain
Switzerland: Depo-Medrol Lidocaine
Thailand: Depo-Medrol with Lidocaine Neo-Medrol
UK: Depo-Medrone with Lidocaine.