DOSAGE AND ADMINISTRATION
The initial dosage of MEDROL 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, MEDROL (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 MEDROL (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it is recommended that it be withdrawn gradually rather than abruptly.
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:
Basic principles and indications for corticosteroid therapy should apply.
The benefits of ADT should not encourage the indiscriminate use of steroids.
ADT is a therapeutic technique primarily designed for patients in whom
long-term pharmacologic corticoid therapy is anticipated.
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.
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.
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).
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
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.
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.
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
MEDROL (methylprednisolone) Tablets are available in the following strengths and package sizes:
2 mg (pink, elliptical, scored, imprinted MEDROL (methylprednisolone) 2)
Bottles of 100
4 mg (white, elliptical, scored, imprinted MEDROL (methylprednisolone) 4)
Bottles of 100
Bottles of 500
Unit dose packages of 100 NDC 0009-0056-05
DOSEPAK™ Unit of Use
(21 tablets) NDC 0009-0056-04
8 mg (peach, elliptical, scored, imprinted MEDROL (methylprednisolone) 8)
Bottles of 25
16 mg (white, elliptical, scored, imprinted MEDROL (methylprednisolone) 16)
Bottles of 50
32 mg (peach, elliptical, scored, imprinted MEDROL (methylprednisolone) 32)
Bottles of 25
Store at controlled room temperature 20° to 25°C (68° to 77°F) [see USP].
Manufactured for: Pharmacia & Upjohn Company., A subsidiary of Pharmacia
Corporation, Kalamazoo, MI 49001, USA
By: MOVA Pharmaceuticals., Manati, PR 00674
Revised May 2002
FDA rev date: 10/25/2002