METHYL PREDNISOLONE SOD SUCCINATE
Composition
SOLU-MEDROL™ Sterile powder 500 mg vial+ Vial
Each 8 ml (when mixed) contains:
Methylprednisolone (as methylprednisolone sodium succinate) 500 mg - Sodium biphosphate -
Dried sodium phosphate • Benzyl alcohol - Water for injection
SOLU-MEDROL." Sterile powder 1000 mg Vial + vial
Each 16 ml (when mixed) contains:
Methylprednisolone (as methylprednisolone sodium succinate) 1000 mg - Sodium biphosphate -
Dried sodium phosphate - Benzyl alcohol ~ Water for injection
properties
DESCRIPTION
This product is an 1.M and IV. injectable form of methylprednisolone, a synthetic
glucocorticosteroid. This highly concentrated aqueous solution is particularly suitable for the
treatment of pathologic conditions, in which an effective and rapid hormonal effect is required.
Methylprednisolone has a strong anti-inflammatorv immunosuppressive and anti-allergic activity.
HUMAN PHARMACODYNAMICS
Clucocorticoids diffuse across cell membranes and complex with specific cytoplasmic receptors,
These complexes then enter the cell nucleus, bind to DNA (chromatini and stimulate transcription
of mRNA and subsequent protein synthesis of various enzymes thought to be ultimately
responsible for the numerous effects of glucocorticoids after systemic use. Clucocorticoids not
only have an important influence on inflammatory and immune processes, but also affect the
carbohydrate, protein and fat metabolism
The anti-inflammatory, immunosuppressive and anti-allergic properties of glucocorticoids are
responsible for most of the therapeutic applications. These properties lead to the following
results:
- reduction of the immunoactive cells near the inflammation focus:
- reduced vasodilation:
- stabilization of the lysosomal membranes:
- inhibition of phagocytosis;
- reduced production of prostaglandins and related substances.
A dose of 4 mg methyiprednisolone has the same glucocorticosteroid (anti-inflammatory) effect
as 20 mg hydrocortisone.
Methylprednisolone has only aminimal mineralocorticoid effect (200 mg methylprednisolone are
equivalent to 1 mg desoxycorticosteronel.
Maximum pharmacologic activity of corticosteroids lags behind peak blood levels, suggesting that
most effects of the drugs result from modification of enzyme activity rather than from direct
actions by the drugs.
HUMAN PHARMACOKINETICS
In vivo, cholinesterases rapidly hydrolyze methylprednisolone sodium succinate to free
methylprednisolone In man. methylprednisolone forms a weak dissociable bond with albumin
and transcortin. Approximately 40 to 90% of the drug is bound.
intravenous infusions with 30 mg/kg. administered over 20 minutes or 1 g administered over 30
to 60 minutes lead after approximately 15 minutes to peak methylprednisolone plasma levels of
nearly 20 ~g/ml. About 25 minutes after an Intravenous bolus injection of 40 mg peak
methylprednisolone plasma values of 42-47 pg/100 ml are measured. Intramuscular injections of
40 mg give peak methylprednisolone plasma levels of 34 ug/lQO ml after some 120 minutes.
intramuscular injections give lower peak values than intravenous injections. With 1.M. injections
plasma values persist for a longer period, with the result that both administration patterns lead
to equivalent quantities of methylprednisolone. The clinical importance of these small differences
is probably minimal when we consider the mechanism of action of glucocorticoids.
A clinical response is usually observed 4 to 6 hours after administration. In the treatment of
asthma, the first beneficial results can already he perceived after 1 or 2 hours. The plasma
half-life of methylprednisolone sodium succinate is 2.3 to 4 hours and appears to bear no
relation to the administration pattern
Methyiprednisolone is a glucocorticoid with a medium-term activity. It has a biological half-life of
12-36 hours The intracellular activity of glucocorticoids resuits in a clear difference between
plasma half-life and pharrnacological half-life. Pharmacological activity persists after measurable
plasma levels have disappeared
The duration of anti-inflammatory activity of glucocorticoids approximately equals the duration
of hypothalamic-pituitary-adrenal (HPA) axis suppression Metabolism of methylprednisolone
occurs via hepatic routes qualitatively similar to that of cortisol. The major metabolites are 20
beta-hydroxymethylprednisolone and 20 beta-hydroxy-6 alpha-rnethylprednisone. The
metabolites are mainly excreted in the urine as glucuronides, sulphates and unconjugated
compounds Following l.v. administration of 14 C labeled methylprednisolone, 75% of the total
radioactivity was recovered in the urine in 96 hours, 9% was recovered in human feces after
5 days and 20% in the bile.
indications
ENDOCRINE DISORDERS
Primary or secondary adrenocortical insufficiency (hydrocortisone or cortisone Is the drug of
choice: synthetic analogues may be used in conjunction with mineralocorticoids where applicable:
in infancy, mineralocorticoid supplementation Is of particular importance.)
Acute adrenocortical insufficiency lhydrocortisone or cortisone is the drug of choice:
mineralocorticoid supplementation may be necessary, particularly when synthetic analogues are
used.)
Preoperatively and in the event of serious trauma or illness, in patients with known adrenal
insufficiency or when adrenocortical reserve is doubtful
Congenital adrenal hyperplasia
Nonsuppurative thyroiditis
Hypercalcaemia associated with cancer
RHEUMATIC DISORDERS
As adjunctive therapy for short-term administration (to tide the patient over an acute episode or
exacerbation) in:
Post-traumatic osteoarthritis
Synovitis of osteoarthritis
Rheumatoid arthritis, including juvenile rheumatoid arthritis (selected cases may require low-dose
maintenance therapy)
Acute and subacute bursitis
Epicondylitis
Acute nonspecific tenosynovitis
Acute gouty arthritis
Psoriatic arthritis
Ankylosing spondylitis
COLLAGEN DISEASES (immune and complex diseases)
During an exacerbation or as maintenance therapy in selected cases of:
Systemic lupus erytriematosus (and lupus nephritis)
Acute rheumatic carditis
Systemic dermatomyositis lpolymyositis)
Polyarteritis nodosa
Good pasture's syndrome
DERMATOLOCIC DISEASES
Pemphigus
Severe erythema multiforme (Stevens-Johnsoh syndrome)
Exfoliative dermatitis
Bullous dermatitis herpetiformis
Severe seborrheic dermatitis
Severe psoriasis
Mycosis fungoides
ALLERGIC STATES
Control of severe or incapacitating allergic conditions intractable to adeguate trials of
conventional treatment in:
Bronchial asthma
Contact dermatitis
Atopic dermatitis
Serum sickness
Seasonal or perennial allergic rhinitis
Drug hypersensitivity reactions
Urticarial transfusion reactions
Acute noninfectious laryngeal edema (epinephrine is the drug of first choice)
OPHTHALMIC DISEASES
Severe acute and chrohic allergic ahd inflammatory processes involving the eye. such as:
Herpes zoster ophthalmicus
Iritis,iridocyclitis
Chorioretinitis
Diffuse posterior uveitis and choroiditis
Optic neuritis
Sympathetic ophthaimia
Anterior segment inflammation
Allergic conjunctivitis
Allergic cornea) marginal ulcers
Keratitis
CASTROINTESTINAL DISEASES
TO tide the patient over a critical period of the disease in
Jlcerative colitis lsystemic therapy)
Regional enteritis (systemic therapy)
RESPIRATORY DISEASES
symptomatic sarcoidosis
Berylliosis
Fulminating or disseminated pulmonary tuberculosis when used concurrently with appropriate
ahtituberculous chemotherapy
Loeffler's syndrome not manageable by other meahS
Aspiration pneumonitis
SOUJ-MFDROI Is beneficial as adjunctive therapy In the treatment of AIDS patients with moderate
to severe Pneuniocysos carinn pneumonia when given within the first 72 hours of Initial
anti-pneumocystis treatment. Due to the ihcreased rate of reactivation of tuberculosis in AIDS
patients, consideration should be given to the administration of antimycobacteria therapy if
corticosteroids are used in this high risk group. The patient should also be observed for
activation of other latent infections.
HEMATOI.OGIC DISORDERS
Acquired (autoimmunel hemolytic anemia
ldiopathic thrombocytopenia purpura in adults (1.V. only; \ M. administration is contraindicated)
Secondary thrombocytopenia In adults
Ervthroblastopenia (R.B.C. anemia)
Congenital (erythroidi hypoplastic anemia
NEOPLASTIC DISEASES
For palliative management of:
Leukemias and lymphomas ih adults
Acute leukemia of childhood
Terminal cancer
To improve quality of life in patients with terminal cancer
EDFMATOUS STATES
To induce diuresis or remission of protelnuria in the nephrotic syndrome, without uremia, of the
idiopathic type or that due to lupus erythematosus
NERVOUS SYSTEM
Cerebral edema from tumor • primary or metastatic and/or associated with surgical or radiation
therapy, or head trauma
Acute exacerbatiohs of multiple sclerosis
Acute spihal cord injury. The treatment should begin within eight hours of ihjury.
CARDIOVASCULAR CONDITIONS
Shock secondary to adrenocortical Insufficiency or shock unresponsive to conventional therapy
when adrenal cortical insufficiehcy may be preseht (hydrocortisone Is generally the drug of
choice When mineralocorticoid activity is undesirable, methylprednisolone may be preferred.)
Although there are no well controlled tdoubleblind placebo) clinical trials, data from experimental
animal models indicate that SOLLI-MEDRQL" Sterile Powder may be useful ih hemorrhagic,
traumatic and surgical shock Uhrespohsive to stahdard therapy (e.g. fluid replacement, etc.). See
also Warning regarding septic shock.
MISCELLANEOUS
Tuberculous meningitis with subarachhoid block or Impending block wheh used concurrently
with appropriate antituberculous chemotherapy
Trichinosis with neurologic or myocardial involvement
organ transplantation
Prevention of nausea and vomiting associated with cancer chemotherapy
Dosage and administration
AS ADJUNCTIVE THERAPY IN LIFE THREATENING CONDITIONS
The recommended dose of SOLU-MEDROL" Sterile Powder lmethylpredhisolOhe sodium succinatel
is iO mg per kg given i.V over a period of at least 30 minutes. This dose may be repeated every
4-6 hours for up to 48 hours
PULSE DOSING for corticosteroid respohsive diseases in exacerbation and/or unresponsive to
standard therapy le.g. lupus hephritis. rheumatoid arthritis, etc.).
Suggested schedules.
Rheumatoid arthritis: 1 g/day 1.V. for 1, 2. 5 or 4 days 1.V. or 1 g/month for 6 mohths 1.V.
Systemic lupus erythematosus: 1 g/day for 3 days I.V.
Multiple sclerosis: 1 g/day for 3 days 1.V. or 1 g/day for 5 days 1.V.
Edematous states, e.g.: glomerulonephritis, lupus nephritis' 50 mg/kg every other day for 4 days
1.V or 1 g/day for 5. 5 or 7 days 1.V.
The regimen should be administered over at least 50 minutes and may be repeated if
improvement has not occurred within a week after therapy or as patient's condition dictates.
TERMINAL CANCER - QUALITY OF LIFE
Prospective, controlled studies have shown that SOLU-MEDROL™ Sterile Powder 125 mg
administered intravenously daily for up to 8 weeks, significantly improves duality of life in
patients with terminal cancer
PREVENTION OF NAUSEA AND VOMITING ASSOCIATED WITH CANCER CHEMOTHERAPY
Suggested schedules'
Mild to moderately emetogenic chemotherapy: Administer SOLU-MEDROL" Sterile Powder 250 mg
l.V. over at least 5 minutes one hour before chemotherapy, at the initiation of chemotherapy and
at the time of discharge. A chlorinated phenothiazine may also be used with the first dose of
SOLU-MEDROL" Sterile Powder for increased effect.
Severely emetogenic chemotherapy: Administer SOLU-MEDROL" Sterile Powder 250 mg I.V. over at
least 5 minutes with appropriate doses of metoclopramide or a butyrophenone one hour before
chemotherapy, then SOLU-MFDROi" Sterile Powder 250 mg 1.v. at the initiation of chemotherapy
and at time of discharge.
ACUTE SPINAL CORD INJURY
For treatment of acute spinal cord injury, administer intravenously 50 mg methylprednisolone per
kilogram of body weight in a bolus dose over a 15 minute period, followed by a 45 minute
pause, and then a continuous Infusion of 5.4 mg/kg per hour for 23 hours. There should be a
separate intravenous site for the infusion pump. The treatment should begin within eight hours
of injury.
PNEUIVIOCYSTIS CARINII PNEUMONIA IN PATIENTS WITH AIDS
A number of dosage schedules have been used. One approach Is to administer 40 mg of
SOLU-MEDROL every 6 to 12 hours with gradual tapering over a maximum of 21 days or until the
end of pneumocystis therapy Therapy should be started within 72 hours of Initial
anti-pneumocystis treatment
IN OTHER INDICATIONS, initial dosage will vary from 10 to 500 mg depending on the clinical
problem being treated. Larger doses may be required for short-term management of severe.
acute conditions. The initial dose, up to 250 mg. should be given intravenously over a period of
at least 5 minutes, and if greater than 250 mg. should be given over at least 50 minutes.
Subseauent doses may be given intravenously or intramusculariy at intervals dictated by the
patients response and clinical condition. Corticosteroid therapy is an adjunct to. and not
replacement for, conventional therapy.
Dosage may be reduced for infants and children but should be governed more by the severity of
the condition and response of the patient than by age or size. It should not be less than 0.5 mg
per kg every 24 hours.
SOLU-MEDROL™ Sterile Powder may be administered by Intravenous or intramuscular injection or
by Intravenous infusion, the preferred method for initial emergency use being intravenous
injection. To administer by intravenous (or intramuscular) injection, prepare solution as directed
INSTRUCTIONS FOR USE
Parenteral drug products should be inspected visually for particulJte matter and discoloration
prior to administration whenever solution and container permit.
a) vial
Under aseptic conditions add the diluent to the vial with sterile powder. Do only use the
special diluent.
bl Preparation of solutions for l.v. infusion
To prepare solutions for intravenous infusion, first reconstitute SOLU-MEDROL" Sterile Powder
as directed. Therapy may be initiated by administering SOLU-MEOROL" Sterile Powder
intravenously over a period of at least five minutes (e.g. doses up to and including 250 mg) to
at least 50 minutes (e.g. doses exceeding 250 mg). Subsequent doses may be withdrawn and
administered similarly. If desired, the medication may be administered in dilute solutions by
admixing the reconstituted product with dextrose 5% in water, normal saline, dextrose 5% in
0.45% or 0.9% sodium chloride. The resulting solutions are physically and chemically stable for
48 hours.
Contra-incUcatlons
Systemic fungal infections
Known hypersensitivity to components
Adverse reactions
FLUID AND ELECTROLYTE DISTURBANCES
Sodium retention, fluid retention, congestive heart failure in susceptible patients, hypertension,
fluid retention, potassium loss and hypokalemic alkalosis
MUSCULOSKELETAL
Steroid myopathy, muscle weakness, osteoporosis, pathologic fractures, vertebral compression
fractures, aseptic necrosis and tendon rupture, particularly of the Achilles tendon.
CASTROINTESTINAL
Peptic ulceration with possible perforation and hemorrhage, gastric hemorrhage, pancreatitis,
esophagitis and perforation of the bowel
DERMATOLOCIC
impaired wound healing, petechiae and ecchymosis and thin fragile skin
METABOLIC
Negative nitrogen balance due to protein catabolism
NEUROLOCICAL
increased intracranial pressure, pseudotumor cerebri. psychic derangements and seizures
ENDOCRINE
Menstrual irregularities, development of Cushingoid state, suppression of pituitary-adrenal axis.
decreased carbohydrate tolerance, manifestation of latent diabetes mellitus. increased
reguirements for insulin or oral hypoglycemic agents in diabetics and suppression of growth in
children
OPHTHALMIC
Posterior subcapsular cataracts, increased intraocular pressure and exophthalmos
IMMUNE SYSTEM
Masking of infections, latent infections becoming active, opportunistic infections, hypersensitivity
reactions including anaphylaxis and may suppress reactions to skin tests
The following additional reactions are related to parenteral corticosteroid therapy:
Anaphylactic allergic reactions with or without circulatory collapse, cardiac arrest, bronchospasm,
cardiac arythmias; hypotension or hypertension
Special precautions
- Recent studies do not establish the efficacy of SOLU-MEDROL" Sterile Powder in septic shock
and suggest that increased mortality may occur in some subgroups at higher risk (i.e. elevated
creatinine greater than 2.0 mgm % or secondary Infections),
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. There may be decreased resistance and inability to localize infection when corticosteroids
are used.
' While on corticosteroid therapy, patients should not be vaccinated against smallpox. Other
immunization procedures should not be undertaken In patients who are on corticosteroids,
especially on high doses, because of possible hazards of neurological complications and lack of
antibody response.
~ The use of SOLU-MEDROI." Sterile Powder 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 appropriate antitubercutous regimen, tf
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 chernoprophylaxis.
- Because rare instances of anaphylactoid {e.g. bronchospasm) reactions have occurred in
patients receiving parenteral corticosteroid therapy, appropriate precautionary measures should
be taken prior to administration, especially when the patient has a history of allergy to any
drug.
~ There are reports of cardiac arythmias and/or circulatory collapse and/or cardiac arrest
following the rapid administration of large 1.V. doses of methylprednisolone sodium succinate
(greater than 0.5 gram administered over a period of less than 10 minutes). Bradycardia has
been reported during or after the administration of large doses of methylprednisotone sodium
succinate and may be unrelated to the speed or duration of infusion
' This product contains benzyl alcohol. Benzyl alcohol has been reported to be associated with a
fatal "Casping syndrome" in premature infants.
- Corticosteroids should be used cautiously in patients with ocular herpes simplex because of
possible corneal perforation.
- 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
- Corticosteroids should be used with caution in nonspecific ulcerative colitis, if there is a
probability of impending perforation, abscess or other pyogenic infection, also in diverticulitis.
fresh intestinal anastomoses, active or latent peptic ulcer, renai insufficiency, hypertension,
osteoporosis or myasthenia gravis.
- 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.
- An acute myopathy has been described with the use of high doses of corticosteroids. most
often occuring in patients with disorders of neuromuscular transmission (eg, myasthenia
gravis!. or in patients receiving concomitant therapy with neuromuscular blocking drugs (eg,
pancuroniumi. This acute myopathy is generalized, may involve ocular and respiratory muscles,
and may result in quadriparesis. Elevations of creatine kinase may occur, clinical improvement
or recovery after stopping corticosteroids may require weeks to years.
- Kaposi's sarcoma has been reported to occur in patients receiving corticosteroid therapy.
Discontinuation of corticosteroids may result in clinical remission
- There is no evidence that corticosteroids are carcinogenic, mutagenic or impair fertility.
DRUG INTERACTIONS
Convulsions have been reported with concurrent use of methylprednisolone and cyclosporin.
Concurrent administration of these agents results in a mutua! inhibition of metabolism.
Therefore it is possible that convulsions and other adverse events associated with the individual
use of either drug may be more apt to occur.
- Combination of glucocosteroids with ulerogenic drugs le.g. salicylates and N.S.A.I.) increase the
risk of gastrointestinal complications
- Combination of qiucocorticosteroids with thiazid-diuretics increases the risk of glucose
intolerance.
- Glucocoticosteroids can increase the requirement for insulin or oral hypoglycemic agents in
diabetics.
- While on corticosteroid therapy, patients should not be vaccinated against smallpox. Other
immunization procedures should not be undertaken in patients who are on corticosteroids.
especially on high doses, because of possible hazards of neurological complications and/or lack
of antibody response.
- Acetylsalicylic acid should be used cautiously in conjunction with corticosteroids in
hypoprothrombinemia.
incompatibilities
The I v conopatibility and stability of methylprednisolone sodium succinate solutions and with
other drugs in intravenous admixtures are dependent on admixture pH, concentration, time,
temperature and the ability of methylprednisolone to solubilize itself. Thus, to avoid compatibility
and stability problems, whenever possible it is recommended that
SOLU-MEDROL." Sterile Powder be administered separately from other drugs and as either 1.V.
push, through an 1.V. medication chamber or as an 1.V. "piggy-back" solution.
Pregnancy and lactation
Some animal studies have shown that corticosteroids, when administered to the mother at high
doses, may cause fetal malformations. Adecluate human reproductive studies have not been
done with corticosteroids. Therefore the use of this drug in pregnancy, nursing mothers or
women of child bearing potential requires that the benefits of the drug be carefully weighed
against the potential risk to the mother and embryo or fetus.
Since there is inadequate evidence of safety in human pregnancy, this drug should be used in
pregnancy only if clearly needed. Corticosteroids readily cross the placenta, infants born of
mothers who have received substantial doses of corticosteroids during pregnancy must be
carefully observed and evaluated for signs of adrenal insufficiency There are no known effects of
corticosteroids on labor and delivery Corticosteroids are excreted in breast milk.
Overdosage
There is no clinical syndrome of acute overdosage with SOLU-MEDROL™ Sterile Powder.
Methylprednisolone is dialyzabie.
Storage
Store unreconstituted product at controlled room temperature 115°-30°C). Store reconstituted
solution at controlled room temperature (15°-SO°C). use solution within 48 hours after mixing.
Manufactured by
Pharmacia N.V./S.A.
Rijksweg 12.
?870 Puurs - Belgium
Marketed by:
Pharmacia India Ltd
SC.O. • 27
Sector 14. Curgaon 122001
HARYANA India