SOLU-MEDRONE INJECTION 40MG

Active substance: METHYLPREDNISOLONE SODIUM SUCCINATE

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Product Summary
1.

NAME OF THE MEDICINAL PRODUCT

Solu-Medrone 40 mg or methylprednisolone sodium succinate for injection.

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION
Solu-Medrone 40 mg : Methylprednisolone sodium succinate 53.0 mg
equivalent to 40 mg of methylprednisolone.

3.

PHARMACEUTICAL FORM
Powder for injection.

4.

CLINICAL PARTICULARS

4.1.

Therapeutic indications
Solu-Medrone is indicated to treat any condition in which rapid and intense
corticosteroid effect is required such as:
1.

Dermatological disease
Severe erythema multiforme (Stevens-Johnson syndrome)

2.

Allergic states
Bronchial asthma
Severe seasonal and perennial allergic rhinitis
Angioneurotic oedema
Anaphylaxis

3.

Gastro-intestinal diseases
Ulcerative colitis
Crohn's disease

4.

Respiratory diseases
Aspiration of gastric contents
Fulminating or disseminated
antituberculous chemotherapy)

5.

tuberculosis

Neurological disorders
Cerebral oedema secondary to cerebral tumour

(with

appropriate

Acute exacerbations of multiple sclerosis superimposed on a relapsingremitting background.
6.

4.2

Miscellaneous
T.B. meningitis (with appropriate antituberculous chemotherapy)
Transplantation

Posology and method of administration
Solu-Medrone may be administered intravenously or intramuscularly, the
preferred method for emergency use being intravenous injection given over a
suitable time interval. When administering Solu-Medrone in high doses
intravenously it should be given over a period of at least 30 minutes. Doses
up to 250 mg should be given intravenously over a period of at least five
minutes.
For intravenous infusion the initially prepared solution may be diluted with
5% dextrose in water, isotonic saline solution, or 5% dextrose in isotonic
saline solution. To avoid compatibility problems with other drugs
Solu-Medrone should be administered separately, only in the solutions
mentioned.
Undesirable effects may be minimised by using the lowest effective dose for
the minimum period (see Other special warnings and precautions).
Parenteral drug products should wherever possible be visually inspected for
particulate matter and discoloration prior to administration.
Adults: Dosage should be varied according to the severity of the condition,
initial dosage will vary from 10 to 500 mg. In the treatment of graft rejection
reactions following transplantation, a dose of up to 1 g/day may be required.
Although doses and protocols have varied in studies using
methylprednisolone sodium succinate in the treatment of graft rejection
reactions, the published literature supports the use of doses of this level, with
500 mg to 1 g most commonly used for acute rejection. Treatment at these
doses should be limited to a 48-72 hour period until the patient's condition has
stabilised, as prolonged high dose corticosteroid therapy can cause serious
corticosteroid induced side-effects (see Undesirable effects and Special
warnings and special precautions for use).
Children: In the treatment of high dose indications, such as haematological,
rheumatic, renal and dermatological conditions, a dosage of 30 mg/kg/day to
a maximum of 1 g/day is recommended. This dosage may be repeated for
three pulses either daily or on alternate days. In the treatment of graft
rejection reactions following transplantation, a dosage of 10 to 20 mg/kg/day
for up to 3 days, to a maximum of 1 g/day, is recommended. In the treatment

of status asthmaticus, a dosage of 1 to 4 mg/kg/day for 1-3 days is
recommended.
Elderly patients: Solu-Medrone is primarily used in acute short-term
conditions. There is no information to suggest that a change in dosage is
warranted in the elderly. However, treatment of elderly patients should be
planned bearing in mind the more serious consequences of the common sideeffects of corticosteroids in old age and close clinical supervision is required
(see Special warnings and special precautions for use).
Detailed recommendations for adult dosage are as follows:
In anaphylactic reactions adrenaline or noradrenaline should be
administered first for an immediate haemodynamic effect, followed by
intravenous injection of Solu-Medrone (methylprednisolone sodium
succinate) with other accepted procedures. There is evidence that
corticosteroids through their prolonged haemodynamic effect are of value in
preventing recurrent attacks of acute anaphylactic reactions.
In sensitivity reactions Solu-Medrone is capable of providing relief within
one half to two hours. In patients with status asthmaticus Solu-Medrone may
be given at a dose of 40 mg intravenously, repeated as dictated by patient
response. In some asthmatic patients it may be advantageous to administer by
slow intravenous drip over a period of hours.
In graft rejection reactions following transplantation doses of up to 1 g
per day have been used to suppress rejection crises, with doses of 500 mg to 1
g most commonly used for acute rejection. Treatment should be continued
only until the patient's condition has stabilised; usually not beyond 48-72
hours.
In cerebral oedema corticosteroids are used to reduce or prevent the cerebral
oedema associated with brain tumours (primary or metastatic).
In patients with oedema due to tumour, tapering the dose of corticosteroid
appears to be important in order to avoid a rebound increase in intracranial
pressure. If brain swelling does occur as the dose is reduced (intracranial
bleeding having been ruled out), restart larger and more frequent doses
parenterally. Patients with certain malignancies may need to remain on oral
corticosteroid therapy for months or even life. Similar or higher doses may
be helpful to control oedema during radiation therapy.
The following are suggested dosage schedules for oedemas due to brain
tumour.
Schedule A (1)

Dose (mg)

Route

Interval
in hours

Pre-operative:
During Surgery:

20
20 to 40

IM
IV

3-6
hourly

Duration

Post operative:

20
16
12
8
4
4
4

IM
IM
IM
IM
IM
IM
IM

3
3
3
3
3
6
12

Schedule B (2)

Dose (mg)

Route

Interval
in hours

Pre-operative:
Post-operative:

40
40
20
12
8
4
4

IM
IM
Oral
Oral
Oral
Oral
Oral

6
6
6
6
8
12

24 hours
24 hours
24 hours
24 hours
24 hours
24 hours
24 hours

Duration

2-3
3-5
1
1
1
1
1

Aim to discontinue therapy after a total of 10 days.
REFERENCES
1.

Fox JL, MD. "Use of Methylprednisolone in Intracranial Surgery"
Medical Annals of the District of Columbia, 34:261-265,1965.

2.

Cantu RC, MD Harvard Neurological Service, Boston, Massachusetts.
Letter on file, The Upjohn Company (February 1970).

In the treatment of acute exacerbations of multiple sclerosis in adults, the
recommended dose is 1 g daily for 3 days. Solu-Medrone should be given as
an intravenous infusion over at least 30 minutes.
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,
doses exceeding 250 mg should be given intravenously over a period of at
least 30 minutes. Subsequent doses may be given intravenously or
intramuscularly at intervals dictated by the patient's response and clinical
condition. Corticosteroid therapy is an adjunct to, and not replacement for,
conventional therapy.

4.3.

Contraindications
Solu-Medrone is contraindicated:
• in patients who have systemic fungal infections unless specific anti-infective
therapy is employed and in cerebral oedema in malaria.
• in patients with known hypersensitivity to methylprednisolone or any component
of the formulation.
• for use by the intrathecal route of administration.
Administration of live or live, attenuated vaccines is contraindicated in patients
receiving immunosuppressive doses of corticosteroids.

4.4.

Special warnings and precautions for use
Immunosuppressant Effects/Increased Susceptibility to Infections
Corticosteroids may increase susceptibility to infection, may mask some signs of
infection, and new infections may appear during their use. Suppression of the
inflammatory response and immune function increases the susceptibility to fungal,
viral and bacterial infections and their severity. The clinical presentation may often
be atypical and may reach an advanced stage before being recognised.
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.
Chickenpox is of serious concern since this normally minor illness may be fatal in
immunosuppressed patients. Patients (or parents of children) without a definite
history of chickenpox should be advised to avoid close personal contact with
chickenpox or herpes zoster and if exposed they should seek urgent medical attention.
Passive immunization with varicella/zoster immunoglobin (VZIG) is needed by
exposed non-immune patients who are receiving systemic corticosteroids or who have
used them within the previous 3 months; this should be given within 10 days of
exposure to chickenpox. If a diagnosis of chickenpox is confirmed, the illness
warrants specialist care and urgent treatment. Corticosteroids should not be stopped
and the dose may need to be increased.
Exposure to measles should be avoided. Medical advice should be sought
immediately if exposure occurs. Prophylaxis with normal intramuscular
immuneglobulin may be needed.
Similarly, corticosteroids should be used with great care in patients with known or
suspected parasitic infections such as Strongyloides (threadworm) infestation, which
may lead to Strongyloides hyperinfection and dissemination with widespread larval
migration, often accompanied by severe enterocolitis and potentially fatal gramnegative septicemia.
Although Solu-Medrone is not approved in the UK for use in any shock indication,
the following warning statement should be adhered to. Data from a clinical study
conducted to establish the efficacy of Solu-Medrone in septic shock, suggest that a

higher mortality occurred in subsets of patients who entered the study with elevated
serum creatinine levels or who developed a secondary infection after therapy began.
Therefore this product should not be used in the treatment of septic syndrome or
septic shock.
The role of corticosteroids in septic shock has been controversial, with early studies
reporting both beneficial and detrimental effects. More recently, supplemental
corticosteroids have been suggested to be beneficial in patients with established septic
shock who exhibit adrenal insufficiency. However, their routine use in septic shock is
not recommended. A systematic review of short-course, high-dose corticosteroids did
not support their use. However, meta-analyses, and a review suggest that longer
courses (5-11 days) of low-dose corticosteroids might reduce mortality.
Live vaccines should not be given to individuals with impaired immune
responsiveness. The antibody response to other vaccines may be diminished.
The use of corticosteroids 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 anti-tuberculous
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.
Kaposi’s sarcoma has been reported to occur in patients receiving corticosteroid
therapy. Discontinuation of corticosteroids may result in clinical remission.
Blood and Lymphatic System
Aspirin and nonsteroidal anti-inflammatory agents should be used cautiously in
conjunction with corticosteroids.
Immune System Effects
Allergic reactions may occur. Rarely skin reactions and anaphylactic/anaphylactoid
reactions have been reported following parenteral Solu-Medrone therapy. Physicians
using the drug should be prepared to deal with such a possibility. Appropriate
precautionary measures should be taken prior to administration, especially when the
patient has a history of drug allergy.
Endocrine Effects
Pharmacologic doses of corticosteroids administered for prolonged periods may result
in hypothalamic-pituitary-adrenal (HPA) suppression (secondary adrenocortical
insufficiency). The degree and duration of adrenocortical insufficiency produced is
variable among patients and depends on the dose, frequency, time of administration,
and duration of glucocorticoid therapy. This effect may be minimized by use of
alternate-day therapy.
In addition, acute adrenal insufficiency leading to a fatal outcome may occur if
glucocorticoids are withdrawn abruptly.
In patients who have received more than physiological doses of systemic
corticosteroids (approximately 6 mg methylprednisolone) for greater than 3 weeks,
withdrawal should not be abrupt.

Drug-induced secondary adrenocortical insufficiency may therefore be minimized by
gradual reduction of dosage. How dose reduction should be carried out depends
largely on whether the disease is likely to relapse as the dose of systemic
corticosteroids is reduced. Clinical assessment of disease activity may be needed
during withdrawal. If the disease is unlikely to relapse on withdrawal of systemic
corticosteroids, but there is uncertainty about HPA suppression, the dose of systemic
corticosteroid may be reduced rapidly to physiological doses. Once a daily dose of 6
mg methylprednisolone is reached, dose reduction should be slower to allow the
HPA-axis to recover.
Abrupt withdrawal of systemic corticosteroid treatment, which has continued up to 3
weeks is appropriate if it considered that the disease is unlikely to relapse. Abrupt
withdrawal of doses up to 32 mg daily of methylprednisolone for 3 weeks is unlikely
to lead to clinically relevant HPA-axis suppression, in the majority of patients. In the
following patient groups, gradual withdrawal of systemic corticosteroid therapy
should be considered even after courses lasting 3 weeks or less:
• Patients who have had repeated courses of systemic corticosteroids, particularly if
taken for greater than 3 weeks.
• When a short course has been prescribed within one year of cessation of longterm therapy (months or years).
• Patients who may have reasons for adrenocortical insufficiency other than
exogenous corticosteroid therapy.
• Patients receiving doses of systemic corticosteroid greater than 32 mg daily of
methylprednisolone.
• Patients repeatedly taking doses in the evening.
Patients should carry 'Steroid Treatment' cards which give clear guidance on the
precautions to be taken to minimise risk and which provide details of prescriber, drug,
dosage and the duration of treatment.
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.
In patients on corticosteroid therapy subjected to unusual stress, increased dosage of
rapidly acting corticosteroids before, during and after the stressful situation is
indicated.
A steroid “withdrawal syndrome,” seemingly unrelated to adrenocortical
insufficiency, may also occur following abrupt discontinuance of glucocorticoids.
This syndrome includes symptoms such as: anorexia, nausea, vomiting, lethargy,
headache, fever, joint pain, desquamation, myalgia, weight loss, and/or hypotension.
These effects are thought to be due to the sudden change in glucocorticoid
concentration rather than to low corticosteroid levels.
Because glucocorticoids can produce or aggravate Cushing’s syndrome,
glucocorticoids should be avoided in patients with Cushing’s disease.
There is an enhanced effect of corticosteroids on patients with hypothyroidism.
Frequent patient monitoring is necessary in patients with hypothyroidism.
Metabolism and Nutrition

Frequent patient monitoring is necessary in patients with diabetes mellitus (or a
family history of diabetes). Corticosteroids, including methylprednisolone, can
increase blood glucose, worsen pre-existing diabetes, and predispose those on longterm corticosteroid therapy to diabetes mellitus.
Psychiatric Effects
Patients and/or carers should be warned that potentially severe psychiatric adverse
reactions may occur with systemic steroids (see section 4.8). Symptoms typically
emerge within a few days or weeks of starting treatment. Risks may be higher with
high doses/systemic exposure (see also section 4.5 ), although dose levels do not
allow prediction of the onset, type, severity or duration of reactions. Most reactions
recover after either dose reduction or withdrawal, although specific treatment may be
necessary. Patients/carers should be encouraged to seek medical advice if worrying
psychological symptoms develop, especially if depressed mood or suicidal ideation is
suspected. Patients/carers should be alert to possible psychiatric disturbances that may
occur either during or immediately after dose tapering/withdrawal of systemic
steroids, although such reactions have been reported infrequently.
Particular care is required when considering the use of systemic corticosteroids in
patients with existing or previous history of severe affective disorders in themselves
or in their first degree relatives. These would include depressive or manic-depressive
illness and previous steroid psychosis.
Frequent patient monitoring is necessary in patients with existing or previous history
of severe affective disorders (especially previous steroid psychosis).
Nervous System Effects
Corticosteroids should be used with caution in patients with seizure disorders.
Frequent patient monitoring is necessary in patients with epilepsy.
Corticosteroids should be used with caution in patients with myasthenia gravis. (Also
see myopathy statement in Musculoskeletal Effects section below.) Frequent patient
monitoring is necessary in patients with myasthenia gravis.
Ocular Effects
Frequent patient monitoring is necessary in patients with glaucoma (or a family
history of glaucoma) and in patients with ocular herpes simplex, for fear of corneal
perforation.
Prolonged use of corticosteroids may produce posterior subcapsular cataracts and
nuclear cataracts (particularly in children), exophthalmos, or increased intraocular
pressure, which may result in glaucoma with possible damage to the optic nerves.
Establishment of secondary fungal and viral infections of the eye may also be
enhanced in patients receiving glucocorticoids.
Cardiac Effects
Adverse effects of glucocorticoids on the cardiovascular system, such as dyslipidemia
and hypertension, may predispose treated patients with existing cardiovascular risk
factors to additional cardiovascular effects, if high doses and prolonged courses are
used. Accordingly, corticosteroids should be employed judiciously in such patients
and attention should be paid to risk modification and additional cardiac monitoring if
needed. Low dose and alternate day therapy may reduce the incidence of
complications in corticosteroid therapy.

There have been a few reports of cardiac arrhythmias and/or circulatory collapse
and/or cardiac arrest associated with the rapid intravenous administration of large
doses of Solu-Medrone (greater than 500 mg administered over a period of less than
10 minutes). Bradycardia has been reported during or after the administration of
large doses of methylprednisolone sodium succinate, and may be unrelated to the
speed and duration of infusion.
Systemic corticosteroids should be used with caution, and only if strictly necessary, in
cases of congestive heart failure.
Care should be taken for patients receiving cardioactive drugs such as digoxin
because of steroid induced electrolyte disturbance/potassium loss (see section 4.8).
Frequent patient monitoring is necessary in patients with congestive heart failure or
recent myocardial infarction (myocardial rupture has been reported).
Vascular Effects
Steroids should be used with caution in patients with hypertension. Frequent patient
monitoring is necessary.
Gastrointestinal Effects
There is no universal agreement on whether corticosteroids per se are responsible for
peptic ulcers encountered during therapy; however, glucocorticoid therapy may mask
the symptoms of peptic ulcer so that perforation or haemorrhage may occur without
significant pain.
Particular care is required when considering the use of systemic corticosteroids in
patients with the following conditions and frequent patient monitoring is necessary.
Ulcerative colitis
Perforation, Abscess or other pyogenic infections
Diverticulitis
Fresh intestinal anastomoses
Peptic ulceration
Hepatobiliary Effects
High doses of corticosteroids may produce acute pancreatitis.
Musculoskeletal Effects
Particular care is required when considering the use of systemic corticosteroids in
patients with myasthenia gravis or osteoporosis (post-menopausal females are
particularly at risk) and frequent patient monitoring is necessary.
Osteoporosis is a common but infrequently recognized adverse effect associated with
a long-term use of large doses of glucocorticoid.
Renal and urinary disorders
Particular care is required when considering the use of systemic corticosteroids in
patients with renal insufficiency and frequent patient monitoring is necessary.
Investigations
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.
Injury, poisoning and procedural complications
Corticosteroids should not be used for the management of head injury or stroke
because it is unlikely to be of benefit and may even be harmful.
Other Adverse Events
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 as to whether daily or intermittent
therapy should be used.
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.
Use in children: Growth and development of infants and children on prolonged
corticosteroid therapy should be carefully observed. Growth may be suppressed in
children receiving long-term, daily, divided-dose glucocorticoid therapy and use of
such regimen should be restricted to the most urgent indications. Alternate-day
glucocorticoid therapy usually avoids or minimizes this side effect.
Infants and children on prolonged corticosteroid therapy are at special risk from
raised intracranial pressure.
High doses of corticosteroids may produce pancreatitis in children.
Use in the elderly: The common adverse effects of systemic corticosteroids may be
associated with more serious consequences in old age, especially osteoporosis,
hypertension, hypokalaemia, diabetes, susceptibility to infection and thinning of the
skin. Caution is recommended with prolonged corticosteroid treatment in the elderly
due to a potential increase risk for osteoporosis, as well as increased risk for fluid
retention with possible resultant hypertension. Close clinical supervision is required
to avoid life-threatening reactions.

4.5

Interaction with other medicinal products and other forms of interaction

Methylprednisolone is a cytochrome P450 enzyme (CYP) substrate and is mainly
metabolized by the CYP3A4 enzyme. CYP3A4 is the dominant enzyme of the most
abundant CYP subfamily in the liver of adult humans. It catalyzes 6β-hydroxylation
of steroids, the essential Phase I metabolic step for both endogenous and synthetic
corticosteroids. Many other compounds are also substrates of CYP3A4, some of
which (as well as other drugs) have been shown to alter glucocorticoid metabolism by
induction (upregulation) or inhibition of the CYP3A4 enzyme.
CYP3A4 INHIBITORS - Drugs that inhibit CYP3A4 activity generally decrease
hepatic clearance and increase the plasma concentration of CYP3A4 substrate
medications, such as methylprednisolone. In the presence of a CYP3A4 inhibitor, the
dose of methylprednisolone may need to be titrated to avoid steroid toxicity.

CYP3A4 INDUCERS - Drugs that induce CYP3A4 activity generally increase
hepatic clearance, resulting in decreased plasma concentration of medications that are
substrates for CYP3A4. Coadministration may require an increase in
methylprednisolone dosage to achieve the desired result.
CYP3A4 SUBSTRATES - In the presence of another CYP3A4 substrate, the hepatic
clearance of methylprednisolone may be inhibited or induced, with corresponding
dosage adjustments required. It is possible that adverse events associated with the use
of either drug alone may be more likely to occur with coadministration.
NON-CYP3A4-MEDIATED EFFECTS – Other interactions and effects that occur
with methylprednisolone are described in Table 2 below.
Table 2 provides a list and descriptions of the most common and/or clinically
important drug interactions or effects with methylprednisolone.
Table 2.
Important drug or substance interactions/effects with
methylprednisolone
Drug Class or Type
- DRUG or SUBSTANCE
Macrolide Antibacterial
- TROLEANDOMYCIN

Interaction

Effect

CYP3A4 INHIBITOR

CYP3A4 INHIBITOR.
An increase in the plasma concentration of
methylprednisolone may occur. The dose of
methylprednisolone may need to be titrated to avoid
steroid toxicity
In addition, there is a potential effect of
methylprednisolone on the acetylation rate and
clearance of isoniazid.

Antibacterial
- ISONIAZID
- GRAPEFRUIT JUICE
Antibiotic, Antitubercular
- RIFAMPIN
Anticonvulsants
- PHENOBARBITAL
- PHENYTOIN

CYP3A4 INDUCER

CYP3A4 INDUCER
A decrease in the plasma concentration of
methylprednisolone may occur. Co-administration
may require an increase in methylprednisolone
dosage to achieve the desired result.

Drug Class or Type
- DRUG or SUBSTANCE
Antiemetic
- APREPITANT
- FOSAPREPITANT

Interaction
CYP3A4
INHIBITORS (and
SUBSTRATES)

Antifungal
- ITRACONAZOLE
- KETOCONAZOLE
Antivirals
- HIV-PROTEASE
INHIBITORS

Effect
CYP3A4 INHIBITORS (and SUBSTRATES)
The hepatic clearance of methylprednisolone may
be inhibited or induced, resulting in an increase or
decrease in the plasma concentration of
methylprednisolone. A corresponding dosage
adjustment may be required. It is possible that
adverse events associated with the use of either
drug alone may be more likely to occur with
administration
Protease inhibitors, such as indinavir and
ritonavir, may increase plasma concentrations of
corticosteroids.

Calcium Channel Blocker
- DILTIAZEM
Contraceptives (oral)
- ETHINYLESTRADIOL /
NORETHISTERONE
Immunosuppressant
- CICLOSPORIN

Ciclosporin
1) Mutual inhibition of metabolism occurs with
concurrent use of ciclosprin and
methylprednisolone, which may increase the
plasma concentrations of either or both drugs.
Therefore, it is possible that adverse events
associated with the use of either drug alone may be
more likely to occur upon coadministration.
2) Convulsions have been reported with concurrent
use of methylprednisolone and ciclosporin.

Macrolide Antibacterial
- CLARITHROMYCIN
- ERYTHROMYCIN

Anticonvulsants
- CARBAMAZEPINE

CYP3A4 INDUCER
(and SUBSTRATE)

Immunosuppressant
- CYCLOPHOSPHAMIDE
- TACROLIMUS

CYP3A4
SUBSTRATES

Anticoagulants (oral)

Non-CYP3A4mediated effects

CYP3A4 INDUCER (and SUBSTRATE)
The hepatic clearance of methylprednisolone may
be inhibited or induced, resulting in an increase or
decrease in the plasma concentration of
methylprednisolone. A corresponding dosage
adjustment may be required. It is possible that
adverse events associated with the use of either
drug alone may be more likely to occur with
administration

CYP3A4 SUBSTRATES
The hepatic clearance of methylprednisolone may
be inhibited or induced, resulting in an increase or
decrease in the plasma concentration of
methylprednisolone. A corresponding dosage
adjustment may be required. It is possible that
adverse events associated with the use of either
drug alone may be more likely to occur with
administration
The effect of methylprednisolone on oral
anticoagulants is variable. There are reports of
enhanced as well as diminished effects of
anticoagulants when given concurrently with
corticosteroids. Therefore, coagulation indices
should be monitored to maintain the desired
anticoagulant effects.

Drug Class or Type
- DRUG or SUBSTANCE
Anticholinergics
- NEUROMUSCULAR
BLOCKERS

Interaction

Antidiabetics

Aromatase inhibitors
- AMINOGLUTETHIMIDE
NSAIDs (nonsteroidal antiinflammatory drugs)
- high-dose ASPIRIN
(acetylsalicylic acid)

Potassium depleting agents
- DIURETICS
- AMPHOTERICIN B
- BETA2 AGONISTS
- XANTHENES

Effect
Corticosteroids may influence the effect of
anticholinergics.
1) An acute myopathy has been reported with the
concomitant use of high doses of corticosteroids
and anticholinergics, such as neuromuscular
blocking drugs. (See section 4.4 Warnings and
Precautions, Musculoskeletal, for additional
information.)
2) Antagonism of the neuromuscular blocking
effects of pancuronium and vecuronium has been
reported in patients taking corticosteroids. This
interaction may be expected with all competitive
neuromuscular blockers.
Because corticosteroids may increase blood glucose
concentrations, dosage adjustments of antidiabetic
agents may be required.
Aminoglutethimide-induced adrenal suppression
may impede endocrine changes caused by
prolonged glucocorticoid treatment.
1) There may be increased incidence of
gastrointestinal bleeding and ulceration when
corticosteroids are given with NSAIDs.
2) Methylprednisolone may increase the clearance
of high-dose aspirin. This decrease in salicylate
serum levels could lead to an increased risk of
salicylate toxicity when methylprednisolone is
withdrawn.
When corticosteroids are administered
concomitantly with potassium depleting agents
patients should be observed closely for
development of hypokalemia.
Corticosteroids antagonize the diuretic effect of
diuretics.

Corticosteroids antagonize the hypotensive effect of all antihypertensives.
There is an increased risk of hypokalaemia when corticosteroids are given with
cardiac glycosides.
The effects of corticosteroids may be reduced for 3-4 days after mifepristone.
Incompatibilities
To avoid compatibility and stability problems, it is recommended that
methylprednisolone sodium succinate be administered separately from other
compounds that are administered via the IV route of administration. Drugs that are
physically incompatible in solution with methylprednisolone sodium succinate
include, but are not limited to: allopurinol sodium, doxapram hydrochloride,
tigecycline, diltiazem hydrochloride, calcium gluconate, vecuronium bromide,
rocuronium bromide, cisatracurium besylate, glycopyrrolate, propofol. (See section
6.2 for additional information.)
4.6

Pregnancy and lactation

Fertility
There is no evidence that corticosteroids impair fertility. In women treatment
with corticosteroids can lead to menstrual irregularities.
Pregnancy
The ability of corticosteroids to cross the placenta varies between individual
drugs, however, methylprednisolone does cross the placenta.
Administration of corticosteroids to pregnant animals can cause abnormalities
of foetal development including cleft palate, intra-uterine growth retardation
and affects on brain growth and development. There is no evidence that
corticosteroids result in an increased incidence of congenital abnormalities,
such as cleft palate in man, however, when administered for long periods or
repeatedly during pregnancy, corticosteroids may increase the risk of intrauterine growth retardation. Hypoadrenalism may, in theory occur in the
neonate following prenatal exposure to corticosteroids but usually resolves
spontaneously following birth and is rarely clinically important. Cataracts
have been observed in infants born to mothers undergoing long-term treatment
with corticosteroids during pregnancy.
As with all drugs, corticosteroids should only be prescribed when the benefits
to the mother and child outweigh the risks. When corticosteroids are essential,
however, patients with normal pregnancies may be treated as though they were
in the non-gravid state.
Lactation
Corticosteroids are excreted in small amounts in breast milk, however, doses
of up to 40 mg daily of methylprednisolone are unlikely to cause systemic
effects in the infant. Infants of mothers taking higher doses than this may
have a degree of adrenal suppression, but the benefits of breast-feeding are
likely to outweigh any theoretical risk.

4.7.

Effects on ability to drive and use machines
The effect of corticosteroids on the ability to drive or use machinery has not been
systematically evaluated. Undesirable effects, such as dizziness, vertigo, visual
disturbances, and fatigue are possible after treatment with corticosteroids. If affected,
patients should not drive or operate machinery.

4.8

Undesirable effects
Under normal circumstances Solu-Medrone therapy would be considered as
short-term. However, the possibility of side-effects attributable to
corticosteroid therapy should be recognised, particularly when high-dose
therapy is being used (see section 4.4). Such side-effects include:

MedDRA
System Organ Class
Infections and infestations

Frequency†

Undesirable Effects

Common

Infection (including increased susceptibility
and severity of infections with suppression
of clinical symptoms and signs).
Opportunistic infection
Recurrence of dormant tuberculosis (see
section 4.4).
Kaposi’s sarcoma has been reported to occur
in patients receiving corticosteroid therapy.
Discontinuation of corticosteroids may
result in clinical remission.
Leucocytosis

Not Known

Neoplasms benign,
malignant and unspecified
(including cysts and polyps

Not Known

Blood and lymphatic
system disorders
Immune system disorders

Not Known

Endocrine disorders

Common
Not Known

Metabolism and nutrition
disorders

Common
Not Known

Not Known

Drug hypersensitivity (including
Anaphylactic reaction and Anaphylactoid
reaction with or without Circulatory
collapse, Cardiac arrest, Bronchospasm)
Cushingoid
Hypopituitarism (including suppression of
the hypothalamo-pituitary-adrenal axis),
Steroid withdrawal syndrome (including,
fever, myalgia, arthralgia, rhinitis,
conjunctivitis, painful itchy skin nodules and
loss of weight)
Sodium retention; Fluid retention
Glucose tolerance impaired; Alkalosis
hypokalaemic; Dyslipidemia, Increased
requirements for insulin (or oral
hypoglycemic agents in diabetics); Negative
nitrogen balance (due to protein catabolism);
Blood urea increased; Increased appetite
(which may result in Weight increased);
Lipomatosis

Psychiatric disorders

Common

Nervous system disorders

Not Known

Eye disorders

Common
Not Known

Ear and labyrinth
disorders
Cardiac disorders

Not Known

Vascular disorders

Common
Not Known
Not Known

Respiratory, thoracic and
mediastinal disorders
Gastrointestinal disorders

Not Known

Common
Not Known

Skin and subcutaneous
tissue disorders

Common
Not Known

A wide range of psychiatric reactions
including affective disorders (such as
irritable, euphoric, depressed and labile
mood psychological dependence and
suicidal thoughts), psychotic reactions
(including mania, delusions, hallucinations
and aggravation of schizophrenia),
behavioural disturbances, irritability,
anxiety, sleep disturbances, and cognitive
dysfunction including confusion and
amnesia have been reported for all
corticosteroids. Reactions are common and
may occur in both adults and children. In
adults, the frequency of severe reactions was
estimated to be 5-6%. Psychological effects
have been reported on withdrawal of
corticosteroids; the frequency is unknown.
Increased intracranial pressure with
Papilloedema [Benign intracranial
hypertension]; Convulsion; Amnesia;
Cognitive disorder; Dizziness; Headache
Posterior subcapsular cataracts
Exophthalmos; Glaucoma; Papilloedema
with possible damage to the optic nerve;
Corneal or scleral thinning; Exacerbation of
ophthalmic viral or fungal disease
Vertigo
Congestive heart failure in susceptible
patients, Arrhythmia
Hypertension
Hypotension; Thrombo-embolism
Hiccups
Peptic ulcer (with possible Peptic ulcer
perforation and Peptic ulcer haemorrhage)
Gastric haemorrhage; Intestinal perforation;
Pancreatitis; Peritonitis; Ulcerative
oesophagitis; Oesophagitis; Oesophageal
candidiasis; Abdominal pain; Abdominal
distension; Diarrhoea; Dyspepsia; Nausea;
Vomiting; Bad taste in mouth may occur
especially with rapid administration
Peripheral oedema; Ecchymosis; Skin
atrophy (thin fragile skin); Acne
Angioedema; Petechiae; Skin striae;
Telangiectasia; Skin hypopigmentation or
hyperpigmentation; Hirsutism; Rash;
Erythema; Pruritus; Urticaria; Hyperhidrosis

Musculoskeletal and
connective tissue disorders

Common
Not Known

Reproductive system and
breast disorders
General disorders and
administration site
conditions

Not Known
Common
Not Known

Investigations

Common
Not Known

Injury, poisoning and
procedural complications

Not Known

Growth retardation (in children);
Osteoporosis; Muscular weakness
Osteonecrosis; Pathological fracture; Muscle
atrophy; Myopathy; Neuropathic
arthropathy; Arthralgia; Myalgia;
Irregular menstruation; Amenorrhoea
Impaired wound healing
Injection site reaction; Fatigue; Malaise;
Withdrawal symptoms - Too rapid a
reduction of corticosteroid dosage following
prolonged treatment can lead to acute
adrenal insufficiency, hypotension and
death. However, this is more applicable to
corticosteroids with an indication where
continuous therapy is given (see Section 4.4)
Blood potassium decreased (potassium loss)
Alanine aminotransferase increased (ALT,
SGPT); Aspartate aminotransferase
increased (AST, SGOT); Blood alkaline
phosphatase increased; Intraocular pressure
increased; Carbohydrate tolerance
decreased; Urine calcium increased;
Suppression of reactions to skin tests
Tendon rupture (particularly of the Achilles
tendon); Spinal compression fracture
(vertebral compression fractures)

† Common (≥1/100 to <1/10); Uncommon (≥1/1,000 to <1/100); Rare
(≥1/10,000 to <1/1,000); Not known (frequency cannot be estimated from the
available data)

4.9.

Overdose
There is no clinical syndrome of acute overdosage with corticosteroids. Reports of
acute toxicity and/or death following overdosage of corticosteroids are rare. In the
event of overdosage, no specific antidote is available; treatment is supportive and
symptomatic. Methylprednisolone is dialysable. Following chronic overdosage the
possibility of adrenal suppression should be guarded against by gradual diminution of
dose levels over a period of time. In such event the patient may require to be
supported during any further stressful episode.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

Pharmacotherapeutic group: Glucorticoids, ATC code: H02AB04
Methylprednisolone is a corticosteroid with an anti-inflammatory activity at least five
times that of hydrocortisone. An enhanced separation of glucocorticoid and
mineralocorticoid effect results in a reduced incidence of sodium and water retention.
5.2

Pharmacokinetic properties

Methylprednisolone pharmacokinetics is linear, independent of route of
administration.
Distribution:
Methylprednisolone is widely distributed into the tissues, crosses the blood-brain
barrier, and is secreted in breast milk. Its apparent volume of distribution is
approximately 1.4 L/kg. The plasma protein binding of methylprednisolone in humans
is approximately 77%.
Metabolism:
Methylprednisolone is extensively bound to plasma proteins, mainly to globulin and
less so to albumin. Only unbound corticosteroid has pharmacological effects or is
metabolised. Metabolism occurs in the liver and to a lesser extent in the kidney. In
humans, methylprednisolone is metabolized in the liver to inactive metabolites; the
major ones are 20α-hydroxymethylprednisolone and 20β-hydroxymethylprednisolone.
Metabolism in the liver occurs primarily via the CYP3A4. (For a list of drug
interactions based on CYP3A4-mediated metabolism, see section 4.5).
Methylprednisolone, like many CYP3A4 substrates, may also be a substrate for the
ATP-binding cassette (ABC) transport protein p-glycoprotein, influencing tissue
distribution and interactions with other medicines.
Elimination:
Metabolites are excreted in the urine.
The mean elimination half-life for total methylprednisolone is in the range of 1.8 to
5.2 hours. Total clearance is approximately 5 to 6 mL/min/kg. Mean elimination halflife ranges from 2.4 to 3.5 hours in normal healthy adults and appears to be
independent of the route of administration.
Total body clearance following intravenous or intramuscular injection of
methylprednisolone to healthy adult volunteers is approximately 15-16l/hour. Peak
methylprednisolone plasma levels of 33.67 mcg/100 ml were achieved in 2 hours after
a single 40 mg I.M. injection to 22 adult male volunteers.
No dosing adjustments are necessary in renal failure. Methylprednisolone is
haemodialysable.

5.3

Preclinical safety data
Based on conventional studies of safety pharmacology and repeated dose
toxicity, no unexpected hazards were identified. The toxicities seen in
repeated-dose studies were those expected to occur with continued exposure to
exogenous adrenocortical steroids.
There was no evidence of a potential for genetic and chromosome mutations in
limited studies performed in bacteria and mammalian cells. Long-term studies
in animals have not been performed to evaluate carcinogenic potential, as the
drug is indicated for short-term treatment only.
Corticosteroids have been shown to be teratogenic in many species when
given in doses equivalent to the human dose. In animal reproduction studies,
glucocorticoids such as methylprednisolone have been shown to induce
malformations (cleft palate, skeletal malformations) and intra-uterine growth
retardation.

6.

PHARMACEUTICAL PARTICULARS

6.1.

List of excipients
Sodium biphosphate and sodium phosphate.
The 40 mg vial also contains lactose.

6.2.

Incompatibilities
None stated.

6.3.

Shelf life
Shelf-life of the medicinal product as packaged for sale: 60 months.
After reconstitution with Sterile Water for injections, use immediately, discard
any remainder.

6.4.

Special precautions for storage
Store below 25°C.

Refer to Section 4.2 Dosage and Administration. No diluents other than those
referred to are recommended. Parenteral drug products should be inspected
visually for particulate matter and discoloration prior to administration.

6.5.

Nature and contents of container
Type I clear glass vial with butyl rubber plug and flip top seal.
Each vial of Solu-Medrone 40 mg contains the equivalent of 40 mg of
methylprednisolone as the sodium succinate for reconstitution with 1 ml of
Sterile Water for Injections.

6.6.

Instruction for use/handling
No special requirements.

7

MARKETING AUTHORISATION HOLDER
Pharmacia Limited
Ramsgate Road
Sandwich
Kent CT13 9NJ

8.

MARKETING AUTHORISATION NUMBER
Solu-Medrone 40 mg PL 0032/0033R

9.
DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
PL 0032/0033R, date of first authorisation: 21 February 1990
Last renewal date: 20 August 1996

10

DATE OF REVISION OF THE TEXT
04/09/2013

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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