Consumer medicine information

Depo-Medrol

Methylprednisolone acetate

BRAND INFORMATION

Brand name

Depo-Medrol

Active ingredient

Methylprednisolone acetate

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Depo-Medrol.

What is in this leaflet

Please read this leaflet carefully before being treated with DEPO-MEDROL suspension for injection. This leaflet answers some common questions about DEPO-MEDROL. It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you being treated with DEPO-MEDROL against the benefits this medicine is expected to have for you.

If you have any concerns about this medicine, ask your doctor or pharmacist.

Consider keeping this leaflet even after treatment with DEPO-MEDROL is finished. You may need to read it again.

What DEPO-MEDROL is used for

DEPO-MEDROL is used to treat disorders of many organ systems such as skin, lung, eye, gastrointestinal tract, nervous system, joints and blood. DEPO-MEDROL works by reducing inflammation and changing the body's natural ability to respond when the immune response is not working properly. It is also used in certain conditions where the adrenal gland doesn't function correctly.

Your doctor may have prescribed DEPO-MEDROL for another reason.

Ask your doctor if you have any questions about why DEPO-MEDROL has been prescribed for you.

This medicine is available only with a doctor's prescription.

Before treatment with DEPO-MEDROL

Some information is provided below. However, always talk to your doctor if you have concerns or questions about your treatment.

When DEPO-MEDROL must not be used

DEPO-MEDROL must not be used:

  1. if you have an allergy to:
  • methylprednisolone acetate
  • any of the other ingredients listed under Product Description at the end of this leaflet.
Symptoms of an allergic reaction may include skin rash, itching or difficulty in breathing.
  1. if you have a severe fungal infection
  2. it must not be injected into the spinal cord (intrathecal or epidural) or into a vein (intravenous)
  3. it must not be given by any other unapproved route of administration
  4. if you have been given a vaccine
  5. if the packaging is torn or shows signs of tampering
  6. after the expiry date (EXP) printed on the carton.
If you use it after the expiry date, it may have no effect at all, or an entirely unexpected effect.

If you are not sure whether you should be treated with DEPO-MEDROL, talk to your doctor.

Before treatment with DEPO-MEDROL

Before treatment with DEPO-MEDROL, tell your doctor if:

  1. you are pregnant or intend to become pregnant
Your doctor will discuss the risks and benefits of using DEPO-MEDROL during pregnancy.
  1. you are breastfeeding or plan to breastfeed
Your doctor will discuss the risks and benefits of using DEPO-MEDROL when breastfeeding.
  1. you have allergies to any other medicines or any other substances such as foods, preservatives or dyes.
  2. you have or have had any of the following:
  • tuberculosis
  • underactive thyroid gland
  • kidney or liver disease
  • herpes in the eye
  • hypoprothrombinaemia (a blood clotting disorder)
  • disease of the bowel, e.g., ulcerative colitis or diverticulitis
  • stomach ulcers
  • diabetes
  • emotional problems or mental disorder
  • any pus-producing infection
  • problems with your heart, including high blood pressure or congestive heart failure
  • Cushing's disease (a hormone disorder)
  • seizure disorders e.g. epilepsy
  • myasthenia gravis (ongoing muscle weakness and chronic fatigue)
  • thin or weak bones, or bones that tend to break easily (osteoporosis)
  • recent head injuries
  • blood clots
  • systemic sclerosis.

Children

Long term treatment with corticosteroids can affect growth and development in children. It can also increase the risk of high pressure in the brain. Your doctor will monitor your child closely if your child needs long term treatment with DEPO-MEDROL.

Elderly

If you are over 65 years old, you may have an increased chance of side effects such as bone weakness possibly leading to fractures. You may also experience fluid retention which may lead to increased blood pressure.

If you have not told your doctor about any of the above, do so before you are treated with DEPO-MEDROL.

Taking other medicines

Tell your doctor if you are taking any other medicines, including medicines that you buy without a prescription from a pharmacy, supermarket or health food shop.

Some medicines or food and DEPO-MEDROL may interfere with each other. Some of these medicines and food include:

  • cyclosporin, cyclophosphamide, tacrolimus (medicines used to suppress the immune system e.g. after a transplant)
  • isoniazid (a medicine to treat tuberculosis)
  • non-steroidal anti-inflammatory drugs [NSAID] such as salicylates or aspirin (medicines used to relieve pain, swelling and other symptoms of inflammation including arthritis)
  • some antifungals e.g. ketoconazole, itraconazole
  • some antibiotics e.g. rifampicin, erythromycin, clarithromycin
  • phenobarbitone, phenytoin, carbamazepine (medicines used to treat epilepsy, convulsions)
  • anticoagulants e.g. warfarin, heparin
  • some immunisations, inoculations or vaccinations
  • some diuretics e.g. frusemide, a medicine to help kidneys get rid of salt and water by increasing the amount of urine produced
  • neuromuscular blocking drugs (medicines that block nerve and muscle action) e.g. pancuronium
  • medicines used to treat myasthenia gravis (ongoing muscle weakness and chronic fatigue), glaucoma, Alzheimer's disease
  • medicines used to treat psychiatric disorders
  • medicines used to treat anxiety
  • bronchodilators (a type of medicine that opens up the airways in the lungs) used to treat asthma, bronchitis, emphysema, and other lung diseases, e.g., salbutamol
  • medicines used to treat diabetes e.g. insulin, glibenclamide and metformin
  • anti-nausea medicines e.g. aprepitant, fosaprepitant
  • medicines to treat HIV e.g. indinavir, ritonavir
  • some medicines to treat blood pressure, heart conditions and stroke, e.g., digoxin and diltiazem
  • oral contraceptives e.g. ethinylestradiol, norethisterone
  • grapefruit juice
  • medicines used to treat breast cancer and hormone disorders.

These medicines and food may be affected by DEPO-MEDROL or may affect how well it works. You may need different amounts of your medicine or you may need to take different medicines.

Your doctor or pharmacist can tell you what to do if you are taking any of these medicines. They also have a more complete list of medicines to be careful with or avoid while being treated with DEPO-MEDROL.

Ask your doctor or pharmacist if you are not sure if you are taking any of these medicines.

Treatment with DEPO-MEDROL

This medicine will be administered under medical supervision.

It may be given into a muscle (intramuscularly) or into a joint (intra-articularly) or into a lesion (intralesional). Due to the risk of serious side effects, it must not be injected into the spinal cord (intrathecally or epidural) or into a vein (intravenously).

How and where DEPO-MEDROL is injected and the dose given will depend on the nature and the severity of your condition. You will be given a different dosage depending on your condition and how you react to the medicine.

If you are given too much (overdose)

Overdose is unlikely with DEPO-MEDROL. However, repeated frequent doses over a long period of time may cause an increase in side effects.

Immediately telephone your doctor or Poisons Information Centre (telephone 13 11 26) for advice, or go to Accident and Emergency (Casualty) at your nearest hospital if you think that you or anyone else may have been given too much DEPO-MEDROL. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention. Keep the telephone numbers for these services handy. Have the DEPO-MEDROL box or this leaflet available to give details if needed.

While you are being treated with it

Things you must do

If you become pregnant while you are being treated with DEPO-MEDROL, tell your doctor.

If you are about to start taking any new medicines, tell your doctor and pharmacist that you are being treated with DEPO-MEDROL.

Tell all doctors, dentists and pharmacists who are treating you that you are being treated with DEPO-MEDROL.

Tell your doctor that you are being treated with DEPO-MEDROL:

  • before having any skin tests
  • before having any kind of surgery
  • if you get a serious injury or infection.

Medicines such as DEPO-MEDROL can increase the risk of infection and mask symptoms of infection.

Tell your doctor if you notice any of the following:

  • fever
  • tiredness
  • sore or swollen joints.

Your doctor may request you follow a low-salt diet and/or take potassium supplements.

If you are a diabetic, your need for insulin or glucose lowering medicines may increase while being treated with DEPO-MEDROL.

For patients having this medicine injected into their joints:

  • be careful not to put too much stress onto that joint for a while
  • ask your doctor how much you can move this joint while it is healing.

Your doctor may reduce the dose of DEPO-MEDROL gradually if you have been on long-term treatment.

Side effects

Check with your doctor as soon as possible if you have any concerns while being treated with DEPO-MEDROL, even if you do not think the concerns are connected with the medicine or are not listed in this leaflet.

Like other medicines, DEPO-MEDROL can cause side effects. If they occur, most are likely to be minor and temporary. However, some may be serious and need medical attention.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor if you notice any of the following and it worries you:

  • nausea
  • vomiting
  • headache or dizziness
  • lightheadedness
  • forgetfulness
  • sleeplessness
  • mood changes e.g. over-excitement, depression, suicidal thoughts, hallucinations, anxiety
  • changes to menstrual periods
  • fluid retention
  • muscle weakness, pain or loss of muscle mass
  • problems with your joints, including pain
  • problems with your growth
  • thin fragile skin or bruising
  • itchy or peeling skin
  • increased sweating
  • facial redness
  • changes to skin at the injection site
  • rashes, acne, hives
  • diarrhoea or constipation
  • heartburn
  • increased appetite
  • loss of appetite or weight loss
  • persistent hiccups
  • tiredness.

Tell your doctor immediately if you experience any of the following

  • bone weakness (can lead to fractures)
  • wounds that will not heal
  • loss in the control of your diabetes
  • red, purple or brown patches on your skin
  • problems with your back, including pain or weakness
  • loss of sensation or problems with your reflexes (slow or too fast)
  • bouts of anxiety and headaches, sweating, palpitations, dizziness, a feeling of weakness, nausea, vomiting, diarrhoea, dilated pupils and blurring vision, stomach pains, and raised blood pressure. These could be symptoms of a rare tumour of the adrenal gland, which sits near the kidney.

Tell your doctor immediately, or go to Accident and Emergency at your nearest hospital if you notice any of the following symptoms:

  • signs of increased pressure in the skull, including drowsiness, vomiting, headache, weakness, numbness and /or eye problems such as double vision
  • allergic type reactions e.g. skin rash, itching and difficulty breathing, wheezing or coughing, chest pain (anaphylactic reaction)
  • signs of infection such as fever, severe chills, sore throat or mouth ulcers
  • severe stomach pains
  • blurred or distorted vision or loss of vision, eye infections
  • breathlessness, fatigue and swelling (heart failure)
  • convulsions or fits
  • passing large amounts of urine, increased thirst and appetite
  • pain and tenderness in the leg, pain on extending the foot, swelling of the lower leg, ankle and foot
  • chest pain and breathlessness.

DEPO-MEDROL can also cause chemical imbalances in the blood, swelling of the pancreas (pancreatitis), masking of infections, increased risk of infection, hormone changes, metabolic changes and changes in liver enzymes, increased blood pressure, increased number of white blood cells (leucocytosis), or cataracts. Some of these side effects can only be found when your doctor does tests to check on your progress.

This is not a complete list of all possible side effects. Some people may get other side effects while being treated with DEPO-MEDROL.

It is very important to tell your doctor if you notice any side effects while being treated with DEPO-MEDROL.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

After treatment with DEPO-MEDROL

Storage

DEPO-MEDROL will normally be stored in a hospital or doctor's surgery. It should be stored in its original packaging in a cool, dry place where the temperature stays below 30°C. It must not be frozen.

Product Description

What it looks like

DEPO-MEDROL is a suspension for injection packaged in a glass vial. It is supplied in cartons of 5 x 1 mL or 1 x 1 mL vials.

Ingredients

The active ingredient in DEPO-MEDROL is methylprednisolone acetate. Each vial contains 40 mg of methylprednisolone acetate.

DEPO-MEDROL also contains macrogol 3350, sodium chloride and miripirium chloride.

Identification

DEPO-MEDROL can be identified by the Australian Register Number, AUST R 12299, which is found on the carton label.

Supplier

DEPO-MEDROL is supplied in Australia by:

Pfizer Australia Pty Ltd
Sydney NSW
Toll free number: 1800 675 229
www.pfizer.com.au

This leaflet was revised in October 2019.

®Registered trademark

© Pfizer Australia Pty Ltd 2013

Published by MIMS December 2019

BRAND INFORMATION

Brand name

Depo-Medrol

Active ingredient

Methylprednisolone acetate

Schedule

S4

 

1 Name of Medicine

Methylprednisolone acetate.

6.7 Physicochemical Properties

Australian Approved Name (AAN): methylprednisolone acetate. Methylprednisolone acetate is a 6-methyl derivative of prednisolone.
Methylprednisolone acetate is a white or practically white, odourless, crystalline powder which melts at about 215°C with some decomposition. It is soluble in dioxane, sparingly soluble in acetone, in alcohol, in chloroform, and in methanol, and slightly soluble in ether. It is practically insoluble in water.
Chemical name: 11β, 17α, 21-trihydroxy-6α-methylpregna-1,4-diene-3,20-dione acetate.
Molecular Formula: C24H32O6.
Molecular weight: 416.51.

Chemical structure.


CAS number.

53-36-1.

2 Qualitative and Quantitative Composition

Depo-Medrol is an anti-inflammatory glucocorticoid, for intramuscular, intra-articular, soft tissue or intralesional injection.
It is available in a 40 mg/mL vial.

3 Pharmaceutical Form

Suspension for Injection.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Naturally occurring glucocorticoids (hydrocortisone), which also have salt retaining properties, are used in replacement therapy in adrenocortical deficiency states. Their synthetic analogues are used primarily for their potent anti-inflammatory effects in disorders of many organ systems. Glucocorticoids cause profound and varied metabolic effects. In addition, they modify the body's immune response to diverse stimuli.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

No data available.

5.3 Preclinical Safety Data

Genotoxicity.

Methylprednisolone actetate has not been formally evaluated for genotoxicity. However, methylprednisolone sulfonate, which is structurally similar to methylprednisolone, was not mutagenic in bacteria (Ames test), or in a mammalian cell gene mutation assay using Chinese hamster ovary cells. Methylprednisolone suleptanate did not induce unscheduled DNA synthesis in primary rat hepatocytes. Prednisolone farnesylate, which is also structurally similar to methylprednisolone, was not mutagenic in bacteria, but displayed weak clastogenic activity in vitro in Chinese hamster lung fibroblasts in the presence of metabolic activation.

Carcinogenicity.

Methylprednisolone has not been formally evaluated in rodent carcinogenicity studies. Negative results for carcinogenicity have been obtained with various other glucocorticoids including budesonide, prednisolone and triamcinolone acetonide, in mice. However, all three of these compounds were shown to increase the incidence of hepatocellular adenomas and carcinomas after oral administration in a 2-year study in male rats. These tumorigenic effects occurred at doses that are less than the typical clinical doses on a mg/m2 basis. Hepatocarcinogenicity is likely to involve an interaction with the glucocorticoid receptor.

4 Clinical Particulars

4.1 Therapeutic 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.

1. Endocrine disorders.

Primary or secondary adrenocortical insufficiency (hydrocortisone or cortisone acetate is the drug of choice; synthetic analogues may be used in conjunction with mineralocorticoids where applicable; in infancy, mineralocorticoid supplementation is of particular importance).
Acute adrenocortical insufficiency (hydrocortisone or cortisone acetate is the drug of choice; mineralocorticoid supplementation may be necessary, particularly when synthetic analogues are used).
Preoperatively and in the event of serious trauma or illness, in patients with known adrenal insufficiency or when adrenocortical reserve is doubtful.
Congenital adrenal hyperplasia.
Hypercalcaemia associated with cancer.
Nonsuppurative thyroiditis.

2. Rheumatic disorders.

As adjunctive therapy for short-term administration (to tide the patient over an acute episode or exacerbation) in post-traumatic osteoarthritis, epicondylitis, synovitis of osteoarthritis, acute nonspecific tenosynovitis, rheumatoid arthritis including juvenile rheumatoid arthritis (selected cases may require low dose maintenance therapy), acute gouty arthritis, psoriatic arthritis, ankylosing spondylitis, acute and subacute bursitis.

3. Collagen diseases.

During an exacerbation or as maintenance therapy in selected cases of systemic lupus erythematosus, acute rheumatic carditis, systemic dermatomyositis (polymyositis).

4. Dermatological diseases.

Pemphigus, bullous dermatitis herpetiformis, severe erythema multiforme (Stevens-Johnson syndrome), severe seborrhoeic dermatitis, exfoliative dermatitis, severe psoriasis, mycosis fungoides.

5. Allergic states.

Control of severe or incapacitating allergic conditions intractable to adequate trials of conventional treatment in bronchial asthma, drug hypersensitivity reactions, contact dermatitis, urticarial transfusion reactions, atopic dermatitis, acute non-infectious laryngeal oedema (adrenaline is the drug of first choice), serum sickness, seasonal or perennial allergic rhinitis.

6. Ophthalmic diseases.

Severe acute and chronic allergic and inflammatory processes involving the eye, such as herpes zoster ophthalmicus, sympathetic ophthalmia, iritis, iridocyclitis, anterior segment inflammation, chorioretinitis, allergic conjunctivitis, diffuse posterior uveitis, allergic corneal marginal ulcers, optic neuritis, keratitis.

7. Gastrointestinal diseases.

To tide the patient over a critical period of the disease in ulcerative colitis (systemic therapy) and regional enteritis (systemic therapy).

8. Respiratory diseases.

Symptomatic sarcoidosis, berylliosis, fulminating or disseminated pulmonary tuberculosis when used concurrently with appropriate anti-tuberculous chemotherapy, aspiration pneumonitis, Loeffler's syndrome not manageable by other means.

9. Haematological disorders.

Acquired (autoimmune) haemolytic anaemia, erythroblastopenia (RBC anaemia), secondary thrombocytopenia in adults, congenital (erythroid) hypoplastic anaemia.

10. Neoplastic diseases.

For palliative management of leukaemias and lymphomas in adults, acute leukaemia in childhood.

11. 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.

12. Nervous system.

Acute exacerbations of multiple sclerosis.

13. Miscellaneous.

Tuberculous meningitis with subarachnoid block or impending block when used concurrently with appropriate anti-tuberculous chemotherapy.
Trichinosis with neurological or myocardial involvement.

B. For intra-articular or soft tissue administration.

Depo-Medrol is indicated as adjunctive therapy for short-term administration (to tide the patient over an acute episode or exacerbation) in synovitis of osteoarthritis, epicondylitis, rheumatoid arthritis, acute non-specific tenosynovitis, acute and subacute bursitis, post-traumatic osteoarthritis, acute gouty arthritis.

C. For intralesional administration.

Depo-Medrol is indicated for intralesional use in the following conditions: keloids, discoid lupus erythematosus, necrobiosis lipoidica diabeticorum, alopecia areata, localised hypertrophic, infiltrated inflammatory lesions of lichen planus, psoriatic plaques, granuloma annulare and lichen simplex chronicus (neurodermatitis).
Depo-Medrol may also be useful in cystic tumours of an aponeurosis or tendon (ganglia).

4.3 Contraindications

Systemic fungal infections.
Known hypersensitivity to methylprednisolone or any component of the formulation.
Intravenous, intrathecal, extradural, epidural or any unspecified route of administration.
Administration of live or live, attenuated vaccines in patients receiving immunosuppressive doses of corticosteroids (see Section 4.4 Special Warnings and Precautions for Use, Immunosuppressant effects/ increased susceptibility to infections).

4.4 Special Warnings and Precautions for Use

The lowest possible dose of corticosteroid should be used to control the condition under treatment, and when reduction in dosage is possible, the reduction must 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.
Methylprednisolone acetate should not be administered by any route other than those listed (see Section 4.1 Therapeutic Indications). It is critical that, during administration of methylprednisolone acetate, appropriate technique be used and care taken to assure proper placement of drug.
Severe medical events have been reported in association with the contraindicated intrathecal/ epidural routes of administration (see Section 4.8 Adverse Effects (Undesirable Effects)). Appropriate measures must be taken to avoid intravascular injection.

Immunosuppressant effects/ increased susceptibility to infections.

Corticosteroids increase susceptibility to infection, may mask some signs of infection, 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 infections, 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.
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.
Do not use intra-articularly, intrabursally or for intratendinous administration for local effect in the presence of acute infection.
A clinical trial in patients with septic shock failed to establish the efficacy of Depo-Medrol for these conditions. Thus, routine use in septic shock is not recommended. The study also suggests that treatment of these conditions with Depo-Medrol may increase the risk of mortality in certain patients (i.e. patients with elevated serum creatinine levels or patients who develop secondary infections after Depo-Medrol).
Administration of live or live attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of corticosteroids. Killed or inactivated vaccines may be administered to patients receiving immunosuppressive doses of corticosteroids, however the response to such vaccines may be diminished. Indicated immunisation procedures may be undertaken in patients receiving non-immunosuppressive doses of corticosteroids.
The use of Depo-Medrol in active tuberculosis should be restricted to those cases of fulminating or disseminated tuberculosis in which the corticosteroid is used for the management of the disease in conjunction with appropriate anti-tuberculosis 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 may occur. Because rare instances of skin reactions and anaphylactic/ anaphylactoid reactions have occurred in patients receiving parenteral corticosteroid therapy, appropriate precautionary measures should be taken prior to administration, especially when the patient has a history of allergy to any drug.
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.

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.
Use of systemic corticosteroid is not recommended in patients with congestive heart failure.

Vascular effects.

Thrombosis including venous thromboembolism has been reported to occur with corticosteroids. As a result corticosteroids should be used with caution in patients who have or may be predisposed to thromboembolic disorders.
Corticosteroids should be used with caution in patients with hypertension.

Endocrine effects.

In patients on corticosteroid therapy subjected to unusual stress, increased dosage of rapidly acting corticosteroids before, during and after the stressful situation is indicated.
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.
In addition, acute adrenal insufficiency leading to a fatal outcome may occur if glucocorticoids are withdrawn abruptly.
Drug induced secondary 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.
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 in patients with hypothyroidism.
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.

Hepatobiliary effects.

Hepatobiliary disorders have been reported which may be reversible after discontinuation of therapy. Therefore appropriate monitoring is required.
There is an enhanced effect of corticosteroids in patients with cirrhosis.

Ocular effects.

Corticosteroids should be used cautiously in patients with ocular herpes simplex because of possible 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 and may enhance the establishment of secondary ocular infections due to fungi or viruses.
Corticosteroid therapy has been associated with central serous chorioretinopathy, which may lead to retinal detachment.
If a patient presents with symptoms such as blurred vision or other visual disturbances, the patient should be considered for referral to an ophthalmologist for evaluation of possible causes.

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.
Potentially severe psychiatric adverse reactions may occur with systemic steroids (see Section 4.8 Adverse Effects (Undesirable Effects)). Symptoms 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.

Gastrointestinal effects.

High doses of corticosteroids may produce acute pancreatitis.
Corticosteroid therapy may mask the symptoms of peptic ulcer so that perforation or haemorrhage may occur without significant pain. Glucocorticoid therapy may mask peritonitis or other signs or symptoms associated with gastrointestinal disorders such as perforation, obstruction or pancreatitis. 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.

Nervous system effects.

Use of corticosteroids is not recommended in patients with seizure disorders.
Corticosteroids should be used with caution in patients with myasthenia gravis (see Section 4.4 Special Warnings and Precautions for Use, 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 corticosteroids affect the ultimate outcome or natural history of the disease. The studies do show that relatively high doses of corticosteroids are necessary to demonstrate a significant effect (see Section 4.2 Dose and Method of Administration).
There have been reports of epidural lipomatosis in patients taking corticosteroids, typically with long-term use at high doses.

Musculoskeletal effects.

An acute myopathy has been described 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 osteoporosis. Osteoporosis is a common but infrequently recognised adverse effect associated with a long-term use of large doses of glucocorticoid.

Metabolism and nutrition.

Corticosteroids, including methylprednisolone, can increase blood glucose, worsen pre-existing diabetes, and predispose those on long-term corticosteroid therapy to diabetes mellitus.

Investigations.

Average and large doses of cortisone or hydrocortisone 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.

Systemic corticosteroids are not indicated for, and should therefore not be used to treat traumatic brain injury. A large multicentre randomised study in patients administered corticosteroid therapy after significant head injury revealed an increased risk of mortality in the corticosteroid group compared to the placebo group.

Other.

Aspirin and non-steroidal anti-inflammatory agents should be used cautiously in conjunction with corticosteroids (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions, NSAIDs).

Additional precautions specific for parenteral corticosteroids.

Intra-articular injection of a corticosteroid may produce systemic as well as local effects.
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 motions, 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.
Sterile technique is necessary to prevent infections or contamination.
The slower rate of absorption by intramuscular administration should be recognised.

Use in renal impairment.

Caution is required in patients with systemic sclerosis because an increased incidence of scleroderma renal crisis has been observed with corticosteroids, including methylprednisolone. Corticosteroids should be used with caution in patients with renal insufficiency.

Use in the elderly.

Caution is recommended with prolonged corticosteroid treatment in the elderly due to a potential increased risk for osteoporosis, as well as increased risk for fluid retention with possible resultant hypertension.

Paediatric use.

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 a regimen should be restricted to the most urgent indications.
Infants and children on prolonged corticosteroid therapy are at special risk from raised intracranial pressure.
High doses of corticosteroids may produce pancreatitis in children.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Methylprednisolone has a wide spectrum of clinical use and is therefore used with numerous concurrent drugs. The interactions summarised in Table 2 are of known or likely clinical significance. The need for dosage adjustment of either medication will depend on the clinical situation, the dose regimen prescribed and the observed clinical response. The interactions listed have either pharmacokinetic or pharmacodynamic basis.
Methylprednisolone is a cytochrome P450 enzyme (CYP) substrate and is mainly metabolised by the CYP3A4 enzyme. CYP3A4 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 concentrations of corticosteroids. Coadministration of these substances may require titration of corticosteroid 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 corticosteroids. Coadministration of these substances may require an increase in corticosteroid 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.
The most common and/or clinically important drug interactions or effects resulting from coadministration of Depo-Medrol and examples of CYP3A4 inhibitors, inducers and substrates are provided in Table 2 and 3. Table 2 and 3 should be used in conjunction with the detailed information provided above.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Animal studies on the effects of methylprednisolone did not show an adverse impact on fertility in male and female rats treated with methylprednisolone aceponate at subcutaneous doses up to 0.1 mg/kg/day, although there was an increase in the number of non-viable fetuses. Other corticosteroids have been shown to impair fertility and reduce embryonic viability in studies in mice and rats.
(Category C)
Corticosteroids have been shown to be teratogenic in many species when given in doses equivalent to the human dose. In animal experiments, corticosteroids (such as methylprednisolone) have been shown to increase the incidence of fetal malformations of various kinds (cleft palate, ventricular septal defect, skeletal malformations), embryo-fetal lethality (e.g. increase in resorptions), intra-uterine growth retardation and abortions. There is limited data on the use of methylprednisolone acetate in human pregnancies, and animal reproduction studies have not been done. Methylprednisolone acetate should be used in pregnancy only after a careful assessment of the benefit/ risk ratio to the mother and fetus.
Corticosteroids readily cross the placenta. Increased incidence of reduced placental and birth weight has been recorded in infants born of mothers receiving corticosteroids.
Infants exposed in utero to substantial doses of corticosteroids must be carefully observed and evaluated for signs of adrenal insufficiency. Since the possibility of suppression of the adrenal cortex in the newborn baby after long-term treatment must be considered, the needs of the mother must be carefully weighed against the risk to the fetus when prescribing corticosteroids.
Cataracts have been observed in infants born to mothers treated with long-term corticosteroids during pregnancy.
The short-term use of corticosteroids antepartum for the prevention of respiratory distress syndrome does not seem to pose a risk to the fetus or the newborn infant. Maternal pulmonary oedema has been reported with tocolysis and fluid overload. No effect is known relating to use in labour and delivery.
Corticosteroids are excreted in breast milk.
Corticosteroids distributed into breast milk may suppress growth and interfere with endogenous glucocorticoid production in nursing infants. This medicinal product should be used during breast feeding only after a careful assessment of the benefit/ risk ratio to the mother and infant.

4.8 Adverse Effects (Undesirable Effects)

Serious undesirable adverse events are also mentioned (see Section 4.4 Special Warnings and Precautions for Use).
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.
The adverse effects are listed in Table 4 by system organ class.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.2 Dose and Method of Administration

Dosage.

Because of possible physical incompatibilities, Depo-Medrol should not be diluted or mixed with other solutions.
Parenteral drug products should be inspected visually for particulate matter and discolouration prior to administration, whenever solution and container permit.
It is critical that, during administration of Depo-Medrol, appropriate technique be used and care taken to assure proper placement of drug.

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 Table 1 are given as a general guide.

Procedure.

It is recommended that the anatomy of the joint involved be reviewed before attempting intra-articular 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 needle has entered the joint space. The injection site for each joint is determined by that 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 not infrequently 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 are 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 steroid therapy, care should be taken to avoid overuse in 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 1% 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 affect disappearance.

Note.

Due to the absence of a true tendon sheath, the Achilles tendon should not be injected with Depo-Medrol.
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 mg 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 effect in dermatological conditions.

Following cleansing with an appropriate antiseptic such as 70% alcohol, 20 mg to 60 mg is injected into the lesion. It may be necessary to distribute doses ranging from 20 mg 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.

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 7, and given as a single 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 bodyweight.
Hormone therapy is an 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 bodyweight, and a chest X-ray should be made at regular intervals during prolonged therapy. Upper gastrointestinal X-rays are desirable in patients with an ulcer history or significant dyspepsia.
In patients with adrenogenital syndrome, a single intramuscular 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 mg to 120 mg.
The usual dosage for patients with skin lesions benefited by systemic corticoid therapy is 40 mg to 120 mg of methylprednisolone acetate administered intramuscularly at weekly intervals for one to four weeks. In chronic contact dermatitis, repeated injections at 5 to 10 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 mg to 120 mg to asthmatic patients, relief may result within 6 to 48 hours and persist for several days to two weeks.
Similarly in patients with allergic rhinitis (hay fever) an intramuscular dose of 80 mg 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 (Solu-Medrol) is indicated.

Multiple sclerosis.

In the treatment of acute exacerbations of multiple sclerosis, daily doses of 200 mg of prednisolone for a week followed by 80 mg every other day for 1 month have been shown to be effective (4 mg of methylprednisolone is equivalent to 5 mg of prednisolone).

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.

4.9 Overdose

Reports of acute toxicity and metabolic disturbances with glucocorticoids are rare but do occur. There is no clinical syndrome of acute overdosage with Depo-Medrol (methylprednisolone acetate). Acute overdose may possibly aggravate pre-existing disease states such as ulceration of the gastrointestinal tract, electrolyte disturbances, infections, diabetes and oedema. Repeated high doses of methylprednisolone have caused hepatic necrosis and an increase in amylase. Bradyarrhythmias, ventricular arrhythmias and cardiac arrest have been observed in cases of intravenous administration of high doses of methylprednisolone.
Repeated frequent doses (daily or several times per week) over a protracted period may result in a Cushingoid state. The possibility of adrenal suppression should be guarded against by gradual diminution of dose levels over a period of time.
In the event of an overdose, treatment is symptomatic and supportive, including respiratory and cardiovascular function. In chronic toxicity, fluids and electrolytes should be monitored closely. Serum levels are not clinically useful.
Depo-Medrol contains macrogol (polyethylene glycol) as an excipient. Hypokalaemia has been reported following an unintentional large intravenous administration of macrogol. In case of overdose, monitor acid balance; renal, cardiac and pulmonary function in symptomatic patients and treat accordingly. Onset of acute lung injury may be delayed.
For information on the management of overdose, contact the Poison Information Centre on 13 11 26 (Australia).

7 Medicine Schedule (Poisons Standard)

S4.

6 Pharmaceutical Particulars

6.1 List of Excipients

Each mL contains: Macrogol 3350 29 mg, sodium chloride 8.7 mg, miripirium chloride (added as preservative) 0.195 mg, water for injections QS.
When necessary, pH is adjusted with sodium hydroxide and/or hydrochloric acid. The pH of the finished product remains within the USP specified range, i.e. 3.0 to 7.0.

6.2 Incompatibilities

Because of possible physical incompatibilities, Depo-Medrol should not be diluted or mixed with other solutions.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Depo-Medrol is for single use in a single patient only. Discard any unused product.
Store below 30°C. Protect from freezing.

6.5 Nature and Contents of Container

Depo-Medrol Suspension for Injection 40 mg per mL supplied as 5 x 1 mL and 1 x 1 mL single dose vials.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

Summary Table of Changes