Methylprednisolone Information
Methylprednisolone (Methylprednisolone) Description
Methylprednisolone (Methylprednisolone) Tablets USP contain Methylprednisolone (Methylprednisolone) which
is a glucocorticoid. Glucocorticoids are adrenocortical steroids, both naturally
occurring and synthetic, which are readily absorbed from the gastrointestinal
tract. Methylprednisolone (Methylprednisolone) occurs as a white to practically white, odorless,
crystalline powder. It is sparingly soluble in alcohol, in dioxane, and in
methanol, slightly soluble in acetone, and in chloroform, and very slightly
soluble in ether. It is practically insoluble in water.
The chemical name for Methylprednisolone (Methylprednisolone) is
11β,17,21-Trihydroxy-6α-methylpregna-1,4-diene-3,20-dione and the molecular
weight is 374.48. The molecular formula is CHO. The structural formula is
represented below:
Each Methylprednisolone (Methylprednisolone) tablet, for oral administration, contains 4 mg of
Methylprednisolone (Methylprednisolone) . In addition, each tablet contains the following inactive
ingredients: anhydrous lactose, croscarmellose sodium, lactose monohydrate,
magnesium stearate, microcrystalline cellulose, polacrilin potassium, sodium
starch glycolate, and stearic acid.
Methylprednisolone (Methylprednisolone) Clinical Pharmacology
Naturally occurring glucocorticoids (hydrocortisone and
cortisone), which also have salt-retaining properties, are used as replacement
therapy in adrenocortical deficiency states. Their synthetic analogs are
primarily used for their potent anti-inflammatory effects in disorders of many
organ systems.
Glucocorticoids cause profound and varied metabolic effects. In addition,
they modify the body’s immune responses to diverse stimuli.
Methylprednisolone (Methylprednisolone) Indications And Usage
Methylprednisolone (Methylprednisolone) Tablets are indicated in the following
conditions:
Methylprednisolone (Methylprednisolone) Contraindications
Systemic fungal infections and known hypersensitivity to
components.
Methylprednisolone (Methylprednisolone) Warnings
In patients on corticosteroid therapy subjected to unusual
stress, increased dosage of rapidly acting corticosteroids before, during, and
after the stressful situation is indicated.
Corticosteroids may mask some signs of infection, and new infections may
appear during their use. Infections with any pathogen including viral,
bacterial, fungal, protozoan or helminthic infections, in any location of the
body, may be associated with the use of corticosteroids alone or in combination
with other immunosuppressive agents that affect cellular immunity, humoral
immunity, or neutrophil function.
These infections may be mild, but can be severe and at times fatal. With
increasing doses of corticosteroids, the rate of occurrence of infectious
complications increases. There may be decreased
resistance and inability to localize infection when corticosteroids are
used.
Prolonged use of corticosteroids may produce posterior subcapsular cataracts,
glaucoma with possible damage to the optic nerves, and may enhance the
establishment of secondary ocular infections due to fungi or viruses.
Average and large doses of hydrocortisone or cortisone can cause elevation of
blood pressure, salt and water retention, and increased excretion of potassium.
These effects are less likely to occur with the synthetic derivatives except
when used in large doses. Dietary salt restriction and potassium supplementation
may be necessary. All corticosteroids increase calcium excretion.
Administration of live or live, attenuated vaccines is contraindicated in
patients receiving immunosuppressive doses of corticosteroids. Killed or
inactivated vaccines may be administered to patients receiving immunosuppressive
doses of corticosteroids; however, the response to such vaccines may be
diminished. Indicated immunization procedures may be undertaken in patients
receiving nonimmunosuppressive doses of corticosteroids.
The use of Methylprednisolone (Methylprednisolone) Tablets in active tuberculosis should be
restricted to those cases of fulminating or disseminated tuberculosis in which
the corticosteroid is used for the management of the disease in conjunction with
an appropriate antituberculous regimen.
If corticosteroids are indicated in patients with latent tuberculosis or
tuberculin reactivity, close observation is necessary as reactivation of the
disease may occur. During prolonged corticosteroid therapy, these patients
should receive chemoprophylaxis.
Persons who are on drugs which suppress the immune system are more
susceptible to infections than healthy individuals. Chicken pox and measles, for
example, can have a more serious or even fatal course in non-immune children or
adults on corticosteroids. In such children or adults who have not had these
diseases particular care should be taken to avoid exposure. How the dose, route
and duration of corticosteroid administration affects the risk of developing a
disseminated infection is not known. The contribution of the underlying disease
and/or prior corticosteroid treatment to the risk is also not known. If exposed,
to chicken pox, prophylaxis with varicella zoster immune globulin (VZIG) may be
indicated. If exposed to measles, prophylaxis with pooled intramuscular
immunoglobulin (IG) may be indicated. (See the respective package inserts for
complete VZIG and IG prescribing information.) If chicken pox develops,
treatment with antiviral agents may be considered. Similarly, corticosteroids
should be used with great care in patients with known or suspected Strongyloides
(threadworm) infestation. In such patients, corticosteroid-induced
immunosuppression may lead to Strongyloides hyperinfection and dissemination
with widespread larval migration, often accompanied by severe enterocolitis and
potentially fatal gram-negative septicemia.
Methylprednisolone (Methylprednisolone) Precautions
Drug-induced secondary adrenocortical insufficiency may be
minimized by gradual reduction of dosage. This type of relative insufficiency
may persist for months after discontinuation of therapy; therefore, in any
situation of stress occurring during that period, hormone therapy should be
reinstituted. Since mineralocorticoid secretion may be impaired, salt and/or a
mineralocorticoid should be administered concurrently.
There is an enhanced effect of corticosteroids on patients with
hypothyroidism and in those with cirrhosis.
Corticosteroids should be used cautiously in patients with ocular herpes
simplex because of possible corneal perforation.
The lowest possible dose of corticosteroid should be used to control the
condition under treatment, and when reduction in dosage is possible, the
reduction should be gradual.
Psychic derangements may appear when corticosteroids are used, ranging from
euphoria, insomnia, mood swings, personality changes, and severe depression, to
frank psychotic manifestations. Also, existing emotional instability or
psychotic tendencies may be aggravated by corticosteroids.
Steroids should be used with caution in nonspecific ulcerative colitis, if
there is a probability of impending perforation, abscess or other pyogenic
infection; diverticulitis; fresh intestinal anastomoses; active or latent peptic
ulcer; renal insufficiency; hypertension; osteoporosis; and myasthenia
gravis.
Growth and development of infants and children on prolonged corticosteroid
therapy should be carefully observed.
Kaposi’s sarcoma has been reported to occur in patients receiving
corticosteroid therapy. Discontinuation of corticosteroids may result in
clinical remission.
Although controlled clinical trials have shown corticosteroids to be
effective in speeding the resolution of acute exacerbations of multiple
sclerosis, they do not show that corticosteroids affect the ultimate outcome or
natural history of the disease. The studies do show that relatively high doses
of corticosteroids are necessary to demonstrate a significant effect. (See .)
Since complications of treatment with glucocorticoids are dependent on the
size of the dose and the duration of treatment, a risk/benefit decision must be
made in each individual case as to dose and duration of treatment and as to
whether daily or intermittent therapy should be used.
Methylprednisolone (Methylprednisolone) Drug Interactions
The pharmacokinetic interactions listed below are potentially
clinically important. Mutual inhibition of metabolism occurs with concurrent use
of cyclosporin and Methylprednisolone (Methylprednisolone) ; therefore, it is possible that adverse
events associated with the individual use of either drug may be more apt to
occur. Convulsions have been reported with concurrent use of Methylprednisolone (Methylprednisolone)
and cyclosporin. Drugs that induce hepatic enzymes such as phenobarbital,
phenytoin and rifampin may increase the clearance of Methylprednisolone (Methylprednisolone) and may
require increases in Methylprednisolone (Methylprednisolone) dose to achieve the desired response.
Drugs such as troleandomycin and ketoconazole may inhibit the metabolism of
Methylprednisolone (Methylprednisolone) and thus decrease its clearance. Therefore, the dose of
Methylprednisolone (Methylprednisolone) should be titrated to avoid steroid toxicity.
Methylprednisolone (Methylprednisolone) may increase the clearance of chronic high dose aspirin.
This could lead to decreased salicylate serum levels or increase the risk of
salicylate toxicity when Methylprednisolone (Methylprednisolone) is withdrawn. Aspirin should be used
cautiously in conjunction with corticosteroids in patients suffering from
hypoprothrombinemia.
The effect of Methylprednisolone (Methylprednisolone) on oral anticoagulants is variable. There
are reports of enhanced as well as diminished effects of anticoagulant when
given concurrently with corticosteroids. Therefore, coagulation indices should
be monitored to maintain the desired anticoagulant effect.
Persons who are on immunosuppressant doses of corticosteroids
should be warned to avoid exposure to chicken pox or measles. Patients should
also be advised that if they are exposed, medical advice should be sought
without delay.
Methylprednisolone (Methylprednisolone) Adverse Reactions
Sodium retention
Congestive heart failure in susceptible patients
Hypertension
Fluid retention
Potassium loss
Hypokalemic alkalosis
Muscle weakness
Loss of muscle mass
Steroid myopathy
Osteoporosis
Tendon rupture, particularly of the Achilles tendon
Vertebral compression fractures
Aseptic necrosis of femoral and humeral heads
Pathologic fracture of long bones
Peptic ulcer with possible perforation and hemorrhage
Pancreatitis
Abdominal distention
Ulcerative esophagitis
Increases in alanine transaminase (ALT, SGPT), aspartate transaminase (AST,
SGOT), and alkaline phosphatase have been observed following corticosteroid
treatment. These changes are usually small, not associated with any clinical
syndrome and are reversible upon discontinuation.
Impaired wound healing
Petechiae and ecchymoses
May suppress reactions to skin tests
Thin fragile skin
Facial erythema
Increased sweating
Increased intracranial pressure with papilledema (pseudo-tumor cerebri)
usually after treatment
Convulsions
Vertigo
Headache
Development of Cushingoid state
Suppression of growth in children
Secondary adrenocortical and pituitary unresponsiveness, particularly in
times of stress, as in trauma, surgery or illness
Menstrual irregularities
Decreased carbohydrate tolerance
Manifestations of latent diabetes mellitus
Increased requirements of insulin or oral hypoglycemic agents in
diabetics
Posterior subcapsular cataracts
Increased intraocular pressure
Glaucoma
Exophthalmos
Negative nitrogen balance due to protein catabolism
The following additional reactions have been reported following oral as well
as parenteral therapy:
Urticaria and other allergic, anaphylactic or hypersensitivity reactions.
Methylprednisolone (Methylprednisolone) Dosage And Administration
The initial dosage of Methylprednisolone (Methylprednisolone) Tablets may vary from 4
mg to 48 mg of Methylprednisolone (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, Methylprednisolone (Methylprednisolone) Tablets should be discontinued and the
patient transferred to other appropriate therapy.
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 (Methylprednisolone) is
equivalent to 5 mg of prednisolone).
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 re-establishment 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 (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:
Methylprednisolone (Methylprednisolone) How Supplied
Methylprednisolone (Methylprednisolone) Tablets USP are supplied as follows:
4 mg tablets: White to off-white, oval tablets debossed and on one side and
quadrisected on the other side, available in
Unit of use
blister packages of 21 NDC 54868-6624-1
Store at controlled room temperature 15° to 30°C (59° to 86°F). [See
USP.]
Dispense in a tight, light-resistant container as defined in USP/NF.
70010609Rev 12/03
Methylprednisolone (Methylprednisolone) Principal Display Panel
4 mg tablets -
Unit of use
blister packages of 21
NDC 54868-6624-1
