The biggest cause of AA in New Zealand

Depo Medrol - New Zealand

Version: pfddepmi10214 Supersedes: pfddepmi10913

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DATA SHEET

DEPO-MEDROL®

Methylprednisolone acetate (40 mg/mL) injection

PRESENTATION

Depo-Medrol is a white, aqueous, sterile suspension containing methylprednisolone acetate 40

mg/mL in a 1 mL vial.

USES

Actions

Methylprednisolone is an anti-inflammatory steroid. Estimates of the relative potencies of

methylprednisolone relative to prednisolone range from 1.13 to 2.1 with an average of 1.5. In

general the required daily dose of methylprednisolone can be estimated to be two thirds (or 0.7)

the required daily dose of prednisolone. While the effect of parenterally administered

methylprednisolone acetate is prolonged, it has the same metabolic and anti-inflammatory actions

as orally administered medicine.

Cortisol and its synthetic analogues, such as methylprednisolone acetate, exert their action locally

by preventing or suppressing the development of local heat, redness, swelling and tenderness by

which inflammation is recognized at the gross level of observation. At the microscopic level,

such compounds inhibit not only the early phenomena of the inflammatory process (oedema,

fibrin deposition, capillary dilation, migration of phagocytes into the inflamed areas and

phagocytic activity), but also the later manifestations (capillary proliferation, fibroblast

proliferation, deposition of collagen and still later cicatrisation). These compounds inhibit

inflammatory response whether the inciting agent is mechanical, chemical or immunological.

Pharmacokinetics

Absorption

Methylprednisolone acetate is hydrolysed to its active form by serum cholinesterases. The

intracellular activity of glucocorticoids results in a clear difference between plasma half-life and

pharmacological 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.

Intramuscular (I.M.) injections of 40 mg/mL give after approximately 7.3 ± 1 hour (Tmax)

methylprednisolone serum peaks of 1.48 ± 0.86 mcg/100 mL (Cmax). The half-life is in this case Version: pfddepmi10214 Supersedes: pfddepmi10913

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DATA SHEET

DEPO-MEDROL®

Methylprednisolone acetate (40 mg/mL) injection

PRESENTATION

Depo-Medrol is a white, aqueous, sterile suspension containing methylprednisolone acetate 40

mg/mL in a 1 mL vial.

USES

Actions

Methylprednisolone is an anti-inflammatory steroid. Estimates of the relative potencies of

methylprednisolone relative to prednisolone range from 1.13 to 2.1 with an average of 1.5. In

general the required daily dose of methylprednisolone can be estimated to be two thirds (or 0.7)

the required daily dose of prednisolone. While the effect of parenterally administered

methylprednisolone acetate is prolonged, it has the same metabolic and anti-inflammatory actions

as orally administered medicine.

Cortisol and its synthetic analogues, such as methylprednisolone acetate, exert their action locally

by preventing or suppressing the development of local heat, redness, swelling and tenderness by

which inflammation is recognized at the gross level of observation. At the microscopic level,

such compounds inhibit not only the early phenomena of the inflammatory process (oedema,

fibrin deposition, capillary dilation, migration of phagocytes into the inflamed areas and

phagocytic activity), but also the later manifestations (capillary proliferation, fibroblast

proliferation, deposition of collagen and still later cicatrisation). These compounds inhibit

inflammatory response whether the inciting agent is mechanical, chemical or immunological.

Pharmacokinetics

Absorption

Methylprednisolone acetate is hydrolysed to its active form by serum cholinesterases. The

intracellular activity of glucocorticoids results in a clear difference between plasma half-life and

pharmacological 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.

Intramuscular (I.M.) injections of 40 mg/mL give after approximately 7.3 ± 1 hour (Tmax)

methylprednisolone serum peaks of 1.48 ± 0.86 mcg/100 mL (Cmax). The half-life is in this case

69.3 hours. After a single I.M. injection of 40 to 80 mg methylprednisolone acetate, duration of

HPA axis suppression ranged from 4 to 8 days. An intra-articular injection of 40 mg in both

knees (total dose: 80 mg) gives after 4 to 8 hours methylprednisolone peaks of approximately

21.5 mcg/100 mL.

Distribution

After intra-articular administration methylprednisolone acetate diffuses from the joint into

systemic circulation over approximately 7 days, as demonstrated by the duration of the HPA axis

suppression and by the serum methylprednisolone values.

In man, methylprednisolone forms a weak dissociable bond with albumin and transcortin.

Approximately 40 to 90% of the drug is bound.

Biotransformation or Metabolism

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-methylprednisone. The metabolites are mainly excreted in the urine as glucuronides,

sulphates and unconjugated compounds. These conjugation reactions occur principally in the

liver and to some extent in the kidney.

INDICATIONS

A. For Intramuscular Administration

When oral therapy is not feasible and the strength, dosage form, and route of administration of the

drug reasonably lend the preparation to the treatment of the condition, the intramuscular use of

Depo-Medrol is indicated as follows:

Endocrine Disorders

 Primary or secondary adrenocortical insufficiency (hydrocortisone or cortisone is the drug of

choice; synthetic analogs may be used in conjunction with mineralocorticoids where

applicable; in infancy; mineralocorticoid supplementation is of particular importance).

 Acute adrenocortical insufficiency (hydrocortisone or cortisone is the drug of choice;

mineralocorticoid supplementation may be necessary, particularly when synthetic analogs are

used).

 Congenital adrenal hyperplasia.

 Hypercalcaemia associated with cancer.

 Nonsuppurative thyroiditis.Version: pfddepmi10214 Supersedes: pfddepmi10913

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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 lowdose

maintenance therapy)

 Acute and subacute bursitis

 Epicondylitis

 Acute nonspecific tenosynovitis

 Acute gouty arthritis

 Psoriatic arthritis

 Ankylosing spondylitis.

Collagen Diseases

During an exacerbation or as maintenance therapy in selected cases of:

 Systemic lupus erythematosus

 Systemic dermatomyositis (polymyositis)

 Acute rheumatic carditis.

Dermatologic Disease

 Pemphigus

 Severe erythema multiforme (Stevens-Johnson Syndrome)

 Exfoliative dermatitis

 Mycosis fungoides

 Bullous dermatitis herpetiformis

 Severe seborrhoeic dermatitis

 Severe psoriasis.Version: pfddepmi10214 Supersedes: pfddepmi10913

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Allergic State

Control of severe or incapacitating allergic conditions intractable to adequate 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 non-infectious laryngeal oedema (adrenaline is the drug of first choice).

Ophthalmic Disease

Severe acute and chronic allergic and inflammatory processes involving the eye, such as:

 Herpes zoster ophthalmicus

 Iritis, iridocyclitis

 Chorioretinitis

 Diffuse posterior uveitis

 Optic neuritis

 Drug hypersensitivity reactions

 Anterior segment inflammation

 Allergic conjunctivitis

 Allergic corneal marginal ulcers

 Keratitis.

Gastrointestional Disease

To tide the patient over a critical period of the disease in:

 Ulcerative colitis

 Regional enteritis.Version: pfddepmi10214 Supersedes: pfddepmi10913

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Respiratory Disease

 Symptomatic sarcoidosis

 Berylliosis

 Fulminating or disseminated pulmonary tuberculosis when used concurrently with appropriate

antituberculous chemotherapy

 Loeffler's Syndrome not manageable by other means

 Aspiration pneumonitis.

Haematologic Disorders

 Acquired (autoimmune) haemolytic anaemia

 Secondary thrombocytopenia in adults

 Erythroblastopenia (RBC anaemia)

 Congenital (erythroid) hypoplastic anaemia.

Neoplastic Disease

For palliative management of:

 Leukemias and lymphomas

 Acute leukaemia of childhood.

Oedematous States

To induce diuresis or remission of proteinuria in the nephrotic syndrome, without uraemia, of the

idiopathic type or that due to lupus erythematosus.

Nervous System

Acute exacerbations of multiple sclerosis.

Miscellaneous

 Tuberculous meningitis with subarachnoid block or impending block when used concurrently

with appropriate antituberculous chemotherapy.

 Trichinosis with neurologic or myocardial involvement.

B. For Intra-articular or Soft Tissue Administration (including Periarticular and

Intrabursal)

As adjunctive therapy for short-term administration (to tide the patient over an acute episode or

exacerbation) in:Version: pfddepmi10214 Supersedes: pfddepmi10913

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 Post-traumatic osteoarthritis

 Synovitis of osteoarthritis

 Rheumatoid arthritis

 Acute and subacute bursitis

 Epicondylitis

 Acute nonspecific tenosynovitis

 Acute gouty arthritis.

C. For Intralesional Administration

Depo-Medrol is indicated for intralesional use in the following conditions:

 Keloids, localised hypertrophic, infiltrated, inflammatory lesions of lichen planus, psoriatic

plaques, granuloma annular, lichen simplex chronicus (neurodermatitis), discoid lupus

erythematosus, Necrobiosis lipoidica diabeticorum, alopecia areata.

 Depo-Medrol may also be useful in cystic tumours of an aponeurosis or tendon (ganglia).

D. For Intrarectal Instillation

 Ulcerative colitis.

DOSAGE AND ADMINISTRATION

Because 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.

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.

Because of possible physical incompatibilities, Depo-Medrol sterile aqueous suspension

(methylprednisolone acetate) should not be diluted or mixed with other solutions.

This product is not suitable for multidose use. Following administration of the desired dose, any

remaining suspension should be discarded.

Parenteral drug products should be inspected visually for particulate matter and discolouration

prior to administration, whenever solution and container permit.

Sterile technique is necessary to prevent infections or contamination.Version: pfddepmi10214 Supersedes: pfddepmi10913

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 Post-traumatic osteoarthritis

 Synovitis of osteoarthritis

 Rheumatoid arthritis

 Acute and subacute bursitis

 Epicondylitis

 Acute nonspecific tenosynovitis

 Acute gouty arthritis.

C. For Intralesional Administration

Depo-Medrol is indicated for intralesional use in the following conditions:

 Keloids, localised hypertrophic, infiltrated, inflammatory lesions of lichen planus, psoriatic

plaques, granuloma annular, lichen simplex chronicus (neurodermatitis), discoid lupus

erythematosus, Necrobiosis lipoidica diabeticorum, alopecia areata.

 Depo-Medrol may also be useful in cystic tumours of an aponeurosis or tendon (ganglia).

D. For Intrarectal Instillation

 Ulcerative colitis.

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Depo-Medrol may be used by any of the following routes: intramuscular, intra-articular,

periarticular, intrabursal, intralesional and into the tendon sheath. It MUST NOT be used

by the intrathecal, epidural or intravenous routes (see CONTRAINDICATIONS,

WARNINGS AND PRECAUTIONS and ADVERSE EFFECTS).

A. Administration for Local Effect

Therapy with Depo-Medrol does not obviate the need for the conventional measures usually

employed. Although this method of treatment will ameliorate symptoms, it is in no sense a cure

and the hormone has no effect on the cause of the inflammation.

1. Rheumatoid and Osteoarthritis

The dose for intra-articular administration depends upon the size of the joint and varies with the

severity of the condition in the individual patient. In chronic cases, injections may be repeated at

intervals ranging from one to five or more weeks, depending upon the degree of relief obtained

from the initial injection. The doses in the following table are given as a general guide:

Size of Joint Examples Range of Dosage

Large Knees, Ankles, Shoulders 20-80 mg

Medium Elbows, Wrists 10-40 mg

Small Metacarpophalangeal

Interphalangeal

Sternoclavicular

Acromioclavicular

4-10 mg

Procedure

It is recommended that the anatomy of the joint involved be reviewed before attempting intraarticular

injection. In order to obtain the full anti-inflammatory effect, it is important that the

injection be made into the synovial space. Employing the same sterile technique as for a lumbar

puncture, a sterile 20 to 24 gauge needle (on a dry syringe) is quickly inserted into the synovial

cavity. Procaine infiltration is elective. The aspiration of only a few drops of joint fluid proves

the joint space has been entered by the needle.

The injection site for each joint is determined by the location where the synovial cavity is most

superficial and most free of large vessels and nerves. With the needle in place, the aspirating

syringe is removed and replaced by a second syringe containing the desired amount of Depo-

Medrol. The plunger is then pulled outward slightly to aspirate synovial fluid and to make sure

the needle is still in the synovial space. After injection, the joint is moved gently a few times to

aid mixing of the synovial fluid and the suspension. The site is covered with a small sterile

dressing.

Suitable sites for intra-articular injection are the knee, ankle, wrist, elbow, shoulder, phalangeal,

and hip joints. Since difficulty is occasionally encountered in entering the hip joint, precautions

should be taken to avoid any large blood vessels in the area.

Joints not suitable for injection are those that are anatomically inaccessible, such as the spinal

joints and those like the sacroiliac joints that are devoid of synovial space. Treatment failures areVersion: pfddepmi10214 Supersedes: pfddepmi10913

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most frequently the result of failure to enter the joint space. Little or no benefit follows injection

into surrounding tissue. If failures occur when injections into the synovial spaces are certain, as

determined by aspiration of fluid, repeated injections are usually futile. Local therapy does not

alter the underlying disease process and, whenever possible, comprehensive therapy including

physiotherapy and orthopaedic correction should be employed.

Following intra-articular corticosteroid therapy care should be taken to avoid overuse of joints in

which symptomatic benefit has been obtained. Negligence in this matter may permit an increase

in joint deterioration that will more than offset the beneficial effects of the steroid.

Unstable joints should not be injected. Repeated intra-articular injection may in some cases result

in instability of the joint. X-ray follow-up is suggested in selected cases to detect deterioration.

If a local anaesthetic is used prior to injection of Depo-Medrol, the anaesthetic package insert

should be read carefully and all the precautions observed.

2. Bursitis

The area around the injection site is prepared in a sterile way and a wheal at the site made with

one percent procaine hydrochloride solution. A 20 to 24 gauge needle attached to a dry syringe is

inserted into the bursa and the fluid aspirated. The needle is left in place and the aspirating

syringe changed for a small syringe containing the desired dose. After injection, the needle is

withdrawn and a small dressing applied.

3. Miscellaneous: Ganglion, Tendinitis, Epicondylitis

In the treatment of conditions such as tendinitis or tenosynovitis, care should be taken, following

application of a suitable antiseptic to the overlying skin, to inject the suspension into the tendon

sheath rather than into the substance of the tendon. The tendon may be readily palpated when

placed on a stretch.

When treating conditions such as epicondylitis, the area of greatest tenderness should be outlined

carefully and the suspension infiltrated into the area. For ganglia of the tendon sheaths, the

suspension is injected directly into the cyst. In many cases a single injection causes a marked

decrease in the size of the cystic tumour and may effect disappearance.

The dose in the treatment of the various conditions of the tendinous or bursal structures listed

above varies with the condition being treated and ranges from 4 to 30 mg. In recurrent or chronic

conditions, repeated injections may be necessary.

The usual sterile precautions should be observed with each injection.

4. Injections for Local Effects in Dermatologic Conditions

Following cleansing with an appropriate antiseptic such as 70% alcohol, 20 to 60 mg of the

suspension is injected into the lesion. It may be necessary to distribute doses ranging from 20 to

40 mg by repeated local injections in the case of large lesions. Care should be taken to avoid

injection of sufficient material to cause blanching since this may be followed by a small slough.

One to four injections are usually employed, the intervals between injections varying with the

type of lesion being treated and the duration of improvement produced by the initial injection.Version: pfddepmi10214 Supersedes: pfddepmi10913

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B. Administration for Systemic Effect

The intramuscular dosage will vary with the condition being treated. When a prolonged effect is

desired, the weekly dose may be calculated by multiplying the daily oral dose by seven and given

as a singular intramuscular injection.

Dosage must be individualised according to the severity of the disease and response of the patient.

For infants and children, the recommended dosage will have to be reduced, but dosage should be

governed by the severity of the condition rather than by strict adherence to the ratio indicated by

age or body weight. Use in children should be limited to the shortest possible time.

Hormone therapy is adjunct to, and not a replacement for, conventional therapy. Dosage must be

decreased or discontinued gradually when the drug has been administered for more than a few

days. The severity, prognosis and expected duration of the disease and the reaction of the patient

to medication are primary factors in determining dosage. If a period of spontaneous remission

occurs in a chronic condition, treatment should be discontinued. Routine laboratory studies, such

as urinalysis, two-hour postprandial blood sugar, determination of blood pressure and body

weight, and a chest X-ray should be made at regular intervals during prolonged therapy. Upper

GI X-rays are desirable in patients with an ulcer history or significant dyspepsia.

In patients with the adrenogenital syndrome, a single intra-muscular injection of 40 mg every two

weeks may be adequate. For maintenance of patients with rheumatoid arthritis, the weekly

intramuscular dose will vary from 40 to 120 mg. The usual dosage for patients with dermatologic

lesions benefited by systemic corticoid therapy is 40 to 120 mg of methyl-prednisolone acetate

administered intramuscularly at weekly intervals for one to four weeks. In acute severe dermatitis

due to poison ivy, relief may result within 8 to 12 hours following intramuscular administration of

a single dose of 80 mg to 120 mg. In chronic contact dermatitis repeated at five to ten day

intervals may be necessary. In seborrhoeic dermatitis, a weekly dose of 80 mg may be adequate

to control the condition.

Following intramuscular administration of 80 to 120 mg to asthmatic patients, relief may result

within six to 48 hours and persist for several days to two weeks. Similarly, in patients with

allergic rhinitis (hay fever), an intramuscular dose of 80 to 120 mg may be followed by relief of

coryzal symptoms within six hours, persisting for several days to three weeks.

If signs of stress are associated with the condition being treated, the dosage of the suspension

should be increased. If a rapid hormonal effect of maximum intensity is required, the intravenous

administration of highly soluble methylprednisolone sodium succinate is indicated.

C. Intrarectal Administration

Depo-Medrol sterile aqueous suspension in doses of 40 to 120 mg administered as retention

enemas or by continuous drip three to seven times weekly for periods of two or more weeks, have

been shown to be a useful adjunct in the treatment of some patients with ulcerative colitis. Many

patients can be controlled with 40 mg of Depo-Medrol sterile aqueous suspension administered in

from 30-300 mL of water depending upon the degree of involvement of the inflamed colonic

mucosa. Other accepted therapeutic measures should, of course, be instituted.Version: pfddepmi10214 Supersedes: pfddepmi10913

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CONTRAINDICATIONS

Known hypersensitivity to methylprednisolone or any component of the formulation.

Systemic fungal infections.

Intrathecal administration due to its potential for neurotoxicity.

Epidural administration.

Intravenous administration as the product is a suspension.

It MUST NOT be used by the intrathecal, epidural, intravenous or any other unspecified

routes.

Administration of live or live, attenuated vaccines is contraindicated in patients receiving

immunosuppressive doses of corticosteroids (see WARNINGS AND PRECAUTIONS,

Immunosuppressive Effects/Increased Susceptibility to Infections).

WARNINGS AND PRECAUTIONS

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. 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.

Administration Precautions

This product is not suitable for multidose use. Following administration of the desired dose, any

remaining suspension should be discarded.

While crystals of adrenal steroids in the dermis suppress inflammatory reactions, their presence

may cause disintegration of the cellular elements and physiochemical changes in the ground

substance of the connective tissue. The resultant infrequently occurring dermal and/or subdermal

changes may form depressions in the skin at the injection site. The degree to which this reaction

occurs will vary with the amount of adrenal steroid injected. Regeneration is usually complete

within a few months or after all crystals of the adrenal steroid have been absorbed.

In order to minimise the incidence of dermal and subdermal atrophy, care must be exercised not

to exceed recommended doses in injections. Multiple small injections into the area of the lesion

should be made whenever possible. The technique of intra-articular and intramuscular injection

should include precautions against injection or leakage into the dermis. Injection into the deltoid

muscle should be avoided because of a high incidence of subcutaneous atrophy.

Depo-Medrol should not be administered by any route other than those listed under

INDICATIONS. It is critical that, during administration of Depo-Medrol, appropriate technique

be used and care taken to assure proper placement of the medicine.Version: pfddepmi10214 Supersedes: pfddepmi10913

Page 11 of 24

Severe medical events have been reported in association with the contraindicated

intrathecal/epidural routes of administration (see ADVERSE EFFECTS). Appropriate measures

must be taken to avoid intravascular injection.

Immunosuppressive Effects/Increased Susceptibility to Infections

Due to their suppression of the inflammatory response and immune function, corticosteroids may

increase susceptibility to fungal, bacterial and viral infections and their severity. Chicken pox and

measles, for example, can have a more serious or even fatal course in non-immune children or

adults on corticosteroids. How the dose, route and duration of corticosteroid administration affect

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, they should seek urgent medical attention. Passive immunisation is recommended if nonimmune

patients who come into contact with chicken pox. If a diagnosis of chicken pox is

confirmed the illness warrants specialist care and urgent treatment.

The immunosuppressive effects of corticosteroids may also result in activation of latent infection

or exacerbation of existing infection. Corticosteroids should be used with great care in patients

with known or suspected parasitic infections such as Strongyloides 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 septicaemia.

It is important to note that corticosteroids may increase susceptibility to infection, may mask

some signs of infection, which may reach an advanced stage before the infection is recognised,

and new infections may appear during their use. There may be decreased resistance and inability

to localise infection when corticosteroids are used. Infections with any pathogen including viral,

bacterial, fungal, protozoan or helminthic organisms, in any location in 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. Caution must therefore be exercised in

patients with HIV/AIDS or diabetes.

Do not use intra-articular, intrabursal or intratendinous administration for local effect in the

presence of acute infection.

Depo-Medrol is not recommended for use in patients with septic shock or sepsis syndrome. 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 and a systematic

review concluded that 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, especially in those with vasopressor-dependent septic shock.

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 suchVersion: pfddepmi10214 Supersedes: pfddepmi10913

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vaccines may be diminished. Indicated immunisation procedures may be undertaken in patients

receiving non-immunosuppressive doses of corticosteroids.

The use of methylprednisolone 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.

Kaposi's sarcoma has been reported to occur in patients receiving corticosteroid therapy.

Discontinuation of corticosteroids may result in clinical remission.

Immune System Effects

Allergic reactions (e.g. angioedema) may occur. Because rare instances of skin reactions and

anaphylactic/anaphylactoid reactions (e.g. bronchospasm) 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. Allergic skin

reactions have been reported apparently related to the excipients in the formulation. Rarely has

skin testing demonstrated a reaction to methylprednisolone acetate, per se.

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 minimised by use of alternate-day therapy.

Symptoms of adrenal insufficiency include: malaise, muscle weakness, mental changes, muscle

and joint pain, desquamation of the skin, dyspnoea, anorexia, nausea and vomiting, fever,

hypoglycaemia, hypotension and dehydration.

Drug-induced adrenocortical insufficiency may be minimised 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.

It is important to note that acute adrenal insufficiency leading to a fatal outcome may occur if

glucocorticoids are withdrawn abruptly. Therefore, withdrawal of corticosteroid should always

be gradual.

In patients on corticosteroid therapy (or those who have discontinued treatment but continue to

experience symptoms of adrenal insufficiency) who are subjected to unusual stress such as

intercurrent illness, trauma or surgery, increased dosage (or reinstitution) of rapidly acting

corticosteroids may be required.Version: pfddepmi10214 Supersedes: pfddepmi10913

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A steroid “withdrawal syndrome”, seemingly unrelated to adrenocortical insufficiency, may 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.

Corticosteroids should be used with caution in patients with hypothyroidism as there is potential

for an enhanced effect of corticosteroids in these patients.

Pheochromocytoma crisis, which can be fatal, has been reported after administration of systemic

corticosteroids. Corticosteroids should only be administered to patients with suspected or

identified pheochromocytoma after an appropriate risk/benefit evaluation.

Metabolism and Nutrition

Corticosteroids, including methylprednisolone, can increase blood glucose, worsen pre-existing

diabetes and predisposes those on long term corticosteroid therapy to diabetes mellitus.

Therefore, corticosteroids should be used with caution in patients with diabetes mellitus or a

family history of diabetes mellitus.

Psychiatric Effects

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. Therefore, particular care is required when considering the use of corticosteroids

in patients with existing or previous history of severe affective disorders.

Symptoms of potentially severe psychiatric adverse reactions associated with corticosteroid use

typically emerge within a few days or weeks of starting treatment. Most reactions recover after

either dose reduction or withdrawal, although specific treatment may be necessary.

Psychological effects have been reported upon withdrawal of corticosteroids; the frequency is

unknown. Patients/caregivers should be encouraged to seek medical attention if psychological

symptoms develop in the patient, especially if depressed mood or suicidal ideation is suspected.

Patients/caregivers should be alert to possible psychiatric disturbances that may occur either

during or immediately after dose tapering/withdrawal of systemic steroids.

Nervous System Effects

Corticosteroids should be used with caution in patients with seizure disorders.

Corticosteroids should be used with caution in patients with myasthenia gravis (see WARNINGS

AND PRECAUTIONS, Musculoskeletal Effects).

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 corticosteroidsVersion: pfddepmi10214 Supersedes: pfddepmi10913

Page 14 of 24

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 DOSAGE

AND ADMINISTRATION).

There have been reports of epidural lipomatosis in patients taking corticosteroids, typically with

long-term use at high doses.

Ocular Effects

Corticosteroids should be used cautiously in patients with ocular herpes simplex because of

possible risk of corneal scarring, loss of vision and 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.

Corticosteroid therapy has been associated with central serous chorioretinopathy, which may lead

to retinal detachment.

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/or prolonged courses are used. When using

corticosteroids in these patients, attention should be paid to risk modification and additional

cardiac monitoring should be considered.

Systemic corticosteroids should be used with caution, and only if strictly necessary, in cases of

congestive heart failure.

Vascular Effects

Corticosteroids should be used with caution in patients with hypertension.

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. In combination with

NSAIDs, the risk of developing gastrointestinal ulcers is increased.

Corticosteroids should be used with caution in non-specific ulcerative colitis, if there is a

probability of impending perforation, abscess or other pyogenic infection, diverticulitis, fresh

intestinal anastomoses, or active or latent peptic ulcer, oesophagitis and gastritis.

Hepatobiliary Effects

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High doses of corticosteroids may produce acute pancreatitis.

There is an enhanced effect of corticosteroids on patients with cirrhosis.

Musculoskeletal Effects

Corticosteroids should be used with caution in patients with myasthenia gravis who are receiving

anticholinesterase therapy as corticosteroid use may decrease plasma anticholinesterase activity.

An acute myopathy has been reported with the use of high doses of corticosteroids, most often

occurring in patients with disorders of neuromuscular transmission (e.g. myasthenia gravis), or in

patients receiving concomitant therapy with anticholinergics, such as neuromuscular blocking

drugs (e.g. pancuronium). This acute myopathy is generalised, 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.

Corticosteroids should be used with caution in patients with osteoporosis. Osteoporosis is a

common but infrequently recognised adverse effect associated with a long-term use of large doses

of glucocorticoid.

Corticosteroid should be used with caution in patients with Duchenne’s muscular dystrophy since

transient rhabdomyolysis and myoglobinuria have been reported following strenuous activities.

Corticosteroids should be used with caution in patients with previous steroid myopathy.

Renal and Urinary Disorders

Corticosteroids should be used with caution in patients with renal insufficiency.

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.

Discontinuation (see WARNINGS AND PRECAUTIONS, Endocrine Effects)

Other

High doses of systemic corticosteroids should not be used for the treatment of traumatic brain

injury.

Aspirin and nonsteroidal anti-inflammatory agents should be used cautiously in conjunction with

corticosteroids (see INTERACTIONS, Other Interactions, NSAIDs).

Additional Precautions Specific For Parenteral Corticosteroids

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Appropriate examination of any joint fluid present is necessary to exclude a septic process.

A marked increase in pain accompanied by local swelling, further restriction of joint motion,

fever, and malaise are suggestive of septic arthritis. If this complication occurs and the diagnosis

of sepsis is confirmed, appropriate antimicrobial therapy should be instituted.

Local injection of a steroid into a previously infected joint is to be avoided.

Corticosteroids should not be injected into unstable joints (see DOSAGE AND

ADMINISTRATION).

Sterile technique is necessary to prevent infections or contamination.

The slower rate of absorption by intramuscular administration should be recognised.

Use in Pregnancy

Corticosteroids have been shown to be teratogenic in many species when given in doses

equivalent to the human dose. Some animal studies have shown that corticosteroids (such as

methylprednisolone), when administered to the mother, may cause foetal malformations of

various kinds (cleft palate, skeletal malformations) and intra-uterine growth retardation.

Adequate human reproductive studies have not been done with corticosteroids. Therefore the use

of this drug in pregnancy, nursing mothers, or women of childbearing potential requires that the

benefits of the drug be carefully weighed against the potential risk to the mother and embryo or

foetus. 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. An increased incidence of low-birth weights in infants

born of mothers receiving corticosteroids has been reported.

Infants born to mothers who have received substantial doses of corticosteroids during pregnancy

must be carefully observed and evaluated for signs of adrenal insufficiency, although neonatal

adrenal insufficiency appears to be rare in infants who were exposed in utero to corticosteroids.

Cataracts have been observed in infants born to mothers treated with long-term corticosteroids

during pregnancy.

Labour and Delivery

There are no known effects of corticosteroids on labour and delivery.

Use in Lactation

Corticosteroids are excreted in breast milk. The potential benefit of treatment must be weighed

against the possible hazards to the infant.

Corticosteroids distributed into breast milk may suppress growth and interfere with endogenous

glucocorticoid production in nursing infants. Since adequate reproductive studies have not been

performed in humans with glucocorticoids, these drugs should be administered to nursing

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Paediatric Use

Growth and development of infants and children on prolonged corticosteroid therapy should be

carefully observed. Corticosteroids may cause growth retardation in infancy, childhood and

adolescence. The effects may be irreversible, therefore, long-term daily divided doses of

corticosteroids should be avoided in these patients.

In infants, children and adolescents, corticosteroid treatment should be administered where

possible as a single dose on alternate days for the shortest possible duration.

Increased intracranial pressure with papilloedema (pseudotumour cerebri) in children has been

reported, usually after treatment withdrawal of methylprednisolone. 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 use of corticosteroids, particularly long-term use, in the elderly should be planned bearing in

mind the more serious consequences in old age, especially osteoporosis, hypertension,

hypokalaemia, diabetes, susceptibility to infection and thinning of the skin. Close clinical

supervision is required to avoid life-threatening reactions.

Use in Renal Impairment

Corticosteroids should be used with caution in patients with renal insufficiency.

Carcinogenicity, Genotoxicity, Effects on Fertility

No evidence exists showing that corticosteroids are carcinogenic, mutagenic or impair fertility.

Effects on Ability to Drive and Use of 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.

ADVERSE EFFECTS

Administration by other than indicated routes has been associated with reports of serious

medical events including: arachnoiditis, meningitis, paraparesis/paraplegia, sensory

disturbances, headache, functional gastrointestinal disorder/bladder dysfunction, seizures,

visual impairment including blindness, ocular and periocular inflammation, and residue or

slough at injection site.

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Infections and Infestations

Not known: Opportunistic infection, infectiona, peritonitis, oesophageal candidiasis, injection

site infectionb.

Blood and lymphatic system disorders

Not known: Leucocytosis.

Immune System Disorders

Not known: Drug hypersensitivity (including anaphylactic reaction and anaphylactoid

reaction).

Endocrine Disorders

Not known: Cushingoid, hypopituitarism, steroid withdrawal syndrome.

Metabolism and Nutrition Disorders

Not known: Lipomatosis, sodium retention, fluid retention, alkalosis hypokalaemic,

dyslipidaemia, glucose tolerance impairedc, increased insulin requirement (or oral

hypoglycaemic agents in diabetics), metabolic acidosis, increased appetite (which

may result in weight increased).

Psychiatric Disorders

Not known: Psychotic disorder (including psychotic behaviour, mania, delusion, hallucination

and schizophrenia), affective disorder (including affect lability, drug dependence,

suicidal ideation, depressed mood, euphoric mood), mental disorder, personality

change, confusional state, anxiety, mood swings, abnormal behaviour, insomnia.

Nervous System Disorders

Not known: Epidural lipomatosis, intracranial pressure increased (with papilloedema [benign

intracranial hypertension]), convulsion, amnesia, cognitive disorder, dizziness,

headache.

Eye Disorders

Not known: Central serous chorioretinopathy, blindnessd, cataract, glaucoma, exophthalmos,

corneal thinning, scleral thinning, exacerbation of ophthalmic viral or fungal

disease.

Ear and Labyrinth Disorders

Not known: Vertigo.

Cardiac Disorders

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Vascular Disorders

Not known: Hypertension, hypotension.

Respiratory, Thoracic and Mediastinal Disorders

Not known: Hiccups.

Gastrointestinal Disorders

Not known: Peptic ulcer (with possible peptic ulcer perforation and peptic ulcer

haemorrhage), intestinal perforation, gastric haemorrhage, pancreatitis,

oesophagitis ulcerative, oesophagitis, abdominal distention, abdominal pain,

diarrhoea, dyspepsia, nausea.

Skin and Subcutaneous Tissue Disorders

Not known: Angioedema, hirsutism, subcutaneous atrophy, skin atrophy, petechiae,

ecchymosis, erythema, hyperhidrosis, pruritus, rash, urticaria, skin striae,

telangiectasia, skin hyperpigmentation, skin hypopigmentation, acne.

Musculoskeletal and Connective Tissue Disorders

Not known: Muscular weakness, myalgia, myopathy, muscle atrophy, osteoporosis,

osteonecrosis, pathological fracture, neuropathic arthropathy, arthralgia, growth

retardation.

Reproductive System and Breast Disorders

Not known: Menstruation irregular, amenorrhoea.

General Disorders and Administration Site Conditions

Not known: Abscess sterile, oedema peripheral, impaired healing, fatigue, malaise, irritability,

injection site reaction, post-injection flaree.

Investigations

Not known: Intraocular pressure increased, carbohydrate tolerance decreased, blood potassium

decreased, nitrogen balance negative (due to protein catabolism), calcium balance

negative, urine calcium increased, alanine aminotransferase increased, aspartate

aminotransferase increased, blood alkaline phosphatase increased, blood urea

increased, suppression of reactions to skin tests.

Injury, Poisoning and Procedural Complications

Not known: Spinal compression fracture, tendon rupturef.

Including increased susceptibility to and severity of infections, masking of infections and latent infections (e.g.

tuberculosis) becoming active.

Following non-sterile administration.

Manifestations of latent diabetes mellitus.

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Following intra-articular use.

Particularly of the Achilles tendon.

INTERACTIONS

The pharmacokinetic interactions listed below are potentially clinically important.

Methylprednisolone is a cytochrome P450 enzyme (CYP) substrate and is metabolised mainly by

the CYP3A4 enzyme. CYP3A4 is the dominant enzyme of the most abundant CYP subfamily in

the liver of adult humans. It catalyses 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, resulting in increased

plasma concentration of methylprednisolone. These include:

 Antifungals such as ketoconazole and itraconazole.

 Antiemetics such as aprepitant and fosaprepitant.

 Immunosuppressants such as ciclosporin. Mutual inhibition of metabolism occurs with

concurrent use of ciclosporin 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.

Convulsions have been reported with concurrent use of methylprednisolone and ciclosporin.

 Macrolide antibacterials such as clarithromycin, erythromycin and troleanomycin.

 HIV-Protease inhibitors such as indinavir and ritonavir, may increase plasma concentrations

of corticosteroids. Corticosteroids may induce the metabolism of HIV-protease inhibitors

resulting in reduced plasma concentrations.

 Calcium channel blockers such as diltiazem.

 Isoniazid may increase the plasma concentration of methylprednisolone. In addition, there is

a potential effect of methylprednisolone to increase the acetylation rate and clearance of

isoniazid.

 Oral contraceptives such as ethinylestradiol and norethisterone, retard the metabolism of

corticosteroids due to increased binding to globulin, resulting in increased plasma levels of

corticosteroids and potentiating their biological effect. The dose of corticosteroids may need

to be adjusted when commencing or stopping oral contraceptive therapy.

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Coadministration of CYP3A4 inhibitors may require titration of methylprednisolone dosage to

reduce the risk of adverse effects and avoid steroid toxicity.

CYP3A4 Inducers

Drugs that induce CYP3A4 activity generally increase hepatic clearance, resulting in decreased

plasma concentrations of methylprednisolone. These include:

 Anticonvulsants such as phenobarbital, phenytoin, carbamazepine and primidone.

 Bactericidal antibiotics such as rifampicin and rifabutin.

Coadministration of these substances 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 affected, 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.

Most CYP3A4 inhibitors are also CYP3A4 substrates.

 Immunosuppressants such as cyclophosphamide and tacrolimus.

Other Interactions

Other interactions and effects that occur with methylprednisolone are described below.

Antacids

Concurrent use may decrease absorption of corticosteroids. Efficacy may be reduced sufficiently

to require dosage adjustments in patients receiving small doses of corticosteroids.

Antidiabetic Agents

Corticosteroids may increase blood glucose levels. Dose adjustments of antidiabetic therapy may

be required with concurrent therapy.

Anticholinergics

Corticosteroids may influence the effect of anticholinergics.

Acute myopathy has been reported with the concomitant use of high doses of corticosteroids and

anticholinergics, such as neuromuscular blocking drugs (see WARNINGS AND

PRECAUTIONS, Musculoskeletal Effects).

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

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Anticholinesterases

Steroids may reduce the effects of anticholinesterases in myasthenia gravis

Anticoagulants (Oral)

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 (such as INR or prothrombin time) should be

monitored to maintain the desired anticoagulant effects.

Aromatase Inhibitors

Aminogluethimide-induced adrenal suppression may exacerbate endocrine changes caused by

prolonged glucocorticoid treatment.

Cardiac Glycosides

There is a risk of toxicity if hypokalaemia occurs due to corticosteroid treatment.

Diuretics and Other Potassium Depleting Agents

Excessive potassium loss maybe experienced with concurrent use of corticosteroids and

potassium depleting diuretics (such as frusemide and thiazides) or carbonic anhydrase inhibitors

(such as acetazolamide). Patients should be observed closely for development of hypokalaemia.

There is also an increased risk of hypokalaemia with concurrent use of corticosteroids with

amphotericin B, xanthenes, or beta2 agonists.

Mifepristone

The effect of corticosteroids may be reduced for 3-4 days after taking mifepristone.

NSAIDs

Concomitant administration may increase the risk of gastrointestinal bleeding and ulceration.

Methylprednisolone may increase the renal clearance of high-dose aspirin, which can lead to

decreased salicylate serum levels. Discontinuation of methylprednisolone treatment can lead to

raised salicylate serum levels, which could lead to an increased risk of salicylate toxicity.

Somatropic

Concomitant administration may inhibit the growth promoting effect of somatropin.

Sympathomimetics

There is an increased risk of hypokalaemia with concurrent high doses of corticosteroids and

sympathomimetics such as salbutamol, salmeterol, terbutaline or formoterol.

Vaccines

Live vaccines should not be given to individuals with impaired immune responsiveness. The

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OVERDOSAGE

There is no clinical syndrome of acute overdosage with Depo-Medrol (methylprednisolone

acetate).

Repeated frequent doses (daily or several times per week) over a protracted period may result in a

Cushingoid state, and other complications of chronic steroid therapy.

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.

Contact the National Poisons Centre on 0800 764 766 for advice on the management of an

overdose.

PHARMACEUTICAL PRECAUTIONS

Depo-Medrol is for single use in a single patient only. Discard any unused product.

Shelf Life

3 years.

Storage Conditions

Store below 30ºC.

MEDICINE CLASSIFICATION

Prescription Medicine.

PACKAGE QUANTITIES

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Page 24 of 24

FURTHER INFORMATION

The chemical name for methylprednisolone acetate is pregna-1,4-diene-3,20-dione, 21-

(acetyloxy)-11,17-dihydroxy-6-methyl-,(6α,11ß).

The structural formula is shown below:

Molecular formula: C24H32O6

Molecular weight: 416.51

CAS Registry Number: 53-36-1.

Excipients

Depo-Medrol contains myristyl-gamma-picolinium chloride (0.02%) as a preservative.

NAME AND ADDRESS

Pfizer New Zealand Ltd

P O Box 3998

Auckland, New Zealand, 1140.

Toll Free Number: 0800 736 363

DATE OF PREPARATION

25 February 2014.

® Depo-Medrol is a registered trademark of Pfizer Inc.