Methylprednisolone
A white or almost white odourless crystalline powder. It ex-
hibits polymorphism.
Practically insoluble in water, soluble I in 100 of alcohol, I
in 800 of chloroform, and I in 800 of ether: slightly soluble
in acetone and in dichloromethane: sparingly soluble in diox-
an and in methyl alcohol. Store in airtight containers. Protect
from light.
Adverse Effects, Treatment, Withdrawal,
and Precautions
As for corticosteroids in general . Rapid
intravenous administration 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 dress-
ings, corticosteroids may be absorbed in sufficient
amounts to cause systemic effects.
References lo various adverse effects associated with intrave-
nous administration of methylprednisolone in high-dose
pulse therapy and to adverse effects following intra-
articular and intranasal administration. Epidural adminis-
tration (or more particularly inadvertent intrathecal adminis-
iralion during attempted epidural placement) may be associated with serious adverse effects including arachnoiditis
and aseptic meningitis, although the degree of risk is un-
certain.
Interactions
The interactions of corticosteroids in general.
Pharmacokinetics
For a brief outline of the pharmacokinetics of corti-
Costeroids in general.
Methylprednisolone is fairly rapidly distributed fol-
lowing administration, 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,
Uses and Administration
Methylprednisolone is a corticosteroid with mainly
glucocorticoid activity, as described under Corticos-
teroids, 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 con-
ditions for which corticosteroid therapy is indicated
except adrenocortical-deficiency
states, for which hydrocortisone with supplementa-
ry fludrocortisone is preferred.
For administration by mouth, methylprednisolone is
usually given in 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 administration in intensive or emer-
gency therapy, methylprednisolone sodium succi-
nate may be administered 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 intra-
muscular or intravenous dose ranges from the equiv-
alent of 10 to 500 mg of methylprednisolone daily.
Large intravenous doses (over 250 mg) should nor-
mally be given slowly over at least 30 minutes; dos-
es 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 given until the patient is stabilised. High
doses given intermittently for a limited period have
sometimes been known as 'pulse therapy' (see un-
der Administration, below) and in graft rejection
I 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
30 mg per kg body-weight 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 per kg per hour
over 24 hours or longer. For slow intravenous infu-
sion methylprednisolone sodium succinate is dis-
solved 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 considera-
bly, depending on the condition: a range of I to
30 mg of methylprednisolone per kg body-weight
daily has been suggested, by the intravenous or in-
tramuscular routes. A total dose of I g daily should
not normally be exceeded.
Methylprednisolone acetate may be administered by
intramuscular injection for a prolonged systemic ef-
fect, 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 aque-
ous suspension is employed. The dose by intra-artic-
ular injection varies from 4 to 80 mg according to
the size of the affected joint. The acetate may also be
administered by intralesional injection in doses of
20 to 60 mg.
For use in the treatment of various skin disorders
methylprednisolone acetate may be applied topical-
ly, usually in concentrations of 0.25 to 1%. The ace-
ponate, which may exhibit modified topical activity,
has also been applied as a 0.1% cream or ointment.
Other esters of methylprednisolone which have oc-
casionally been used include the cypionate and the
suleptanate.
Administration. For short-term intensive therapy or in cer-
tain emergency situations a technique of corticosteroid ad-
ministration known as 'pulse therapy' has been employed.
Methylprednisolone has often been used in this manner and
typically high doses of about I g intravenously have been giv-
en, usually daily or on alternate days, or weekly, for a limited
number of doses: the most common regimen appears to be 1 gm
daily for 3 days.
Blood disorders. Methylprednisolone is one of the corti-
costeroids that have been used in the management of haeman-
gioma and the Kasabach-Meiritt syndrome.
There is also a report of benefit from very high-dose therapy
in a few patients with refractory red cell aplasia due to Black-
fan-Diamond anemia.
IDIOPATHIC THROMBOCYTOPENIC PURPUKA. High dose methyl-
prednisolone may be employed as part of the emergency man-
agement of acute idiopathic thrombocytopenic purpura, for
example when major acute bleeding or intracranial haemor-
rhage supervene, and has also been used by mouth or intrave-
nously in the management of the chronic form, although
prednisolone or prednisone are more frequently used for oral
therapy.
Bone disorders. For mention of injection of methylpred-
nisolone into bone cysts to stimulate bone formation, see
literature.
Glomerular kidney disease. For a discussion of the vari-
ous forms of glomerular kidney disease and their manage-
ment see literature.
Multiple sclerosis. Methylprednisolone is one of the corti-
costeroids used in multiple sclerosis, the management of
which is discussed further.
Polymyalgia rheumatica: For mention of the use of meth-
ylprednisolone to treat polymyalgia rheumatica see lit.
Rheumatoid arthritis. Methylprednisolone administered
in intravenous pulses has been reported to be effective in the
treatment of rheumatoid arthritis. Some studies have shown
this treatment to be of greatest benefit when given concomi-
lantly with a disease modifying antirheumatic drug
(DMARD) such as gold, although some showed the addi-
tion of methylprednisolone to existing therapy lo have no ex-
tra benefit.' A comparatively low dose of 100 mg was found
to be as effective as 1000 mg in one study. Monthly admin-
istration of methylprednisolone by deep intramuscular injec-
tion was also an effective adjunct to gold therapy. In general.
however, the use of corticosteroids in rheumatoid arthritis is
controversial. Systemic corticosteroids can suppress symp-
toms of the disease, but their usefulness is limited by their
adverse effects and they are usually reserved for severe rapid-
ly progressing disease unresponsive to conventional therapy,
to control disease activity during initiation of therapy with a
DMARD, or in disease accompanied by severe extra-articular
effects. Intra-articular injection has been used for joints af-
fected by an acute flare but should be given infrequently.
For a discussion of the management of rheumatoid arthritis,
including the use of corticosteroids, see p.2.
Systemic lupus erythematosus. Pulsed intravenous
methylprednisolone is used in the management of lupus ne-
phritis. alone or combined with immunosuppressants. For
discussion of the management of systemic lupus erythemato-
sus including the role of methylprednisolone, see lit.
Vertigo. In a double-blind study, 9 of 10 patients treated with
methylprednisolone 32 mg by mouth, on day one followed by
16 mg twice daily for 3 days and then tapered off and stopped
after 8 days showed improvement in symptoms of acute ves-
tibular vertigo. Three of 10 patients receiving placebo im
proved initially, and 7 improved after transferring to
methylprednisolone treatment. However, corticosteroids are
not one of the usual classes of drugs employed in the treat,
ment of vertigo, which usually depends on antihista-
mines or phenothiazines for its management.