Consumer medicine information

Methylpred

Methylprednisolone sodium succinate

BRAND INFORMATION

Brand name

Methylpred

Active ingredient

Methylprednisolone sodium succinate

Schedule

What is in this leaflet

This leaflet answers some common questions about METHYLPRED. 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 given METHYLPRED against the benefits they expect it will have for you.

Follow the instructions given to you by your doctor and advice contained in this leaflet.

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

Keep this leaflet with the medicine. You may need to read it again.

What METHYLPRED is used for

METHYLPRED contains methylprednisolone (as methylprednisolone sodium succinate) as the active ingredient. It belongs to a group of medicines called corticosteroids.

It is used for the treatment of one or more of the following conditions:

skin diseases
allergic reactions
inflammation of the eyes
respiratory diseases and certain respiratory infections
diseases of the gut (gastrointestinal tract)
multiple sclerosis
rheumatic disorders
diseases of the blood
treatment of certain glandular conditions

How your medicine works

METHYLPRED reduces inflammation (pain, swelling, redness and heat) which is one of the body's reactions to injury and by reducing the body's reaction to infection.

Ask your doctor if you have any questions about why this medicine has been prescribed for you. Your doctor may have prescribed it for another purpose.

It is available only with a doctor's prescription.

There is no evidence that it is addictive.

Before you are given it

When Methylpred must not be used

You must not be given METHYLPRED if you have an allergy to:

any medicine containing methylprednisolone sodium succinate
any of the ingredients listed at the end of this leaflet.

The METHYLPRED 40 mg product contains lactose from cow's milk.

Tell your doctor if you are allergic or suspect you are allergic to cow's milk or to any other dairy products. Some symptoms of an allergic reaction may include rash, itching or hives on the skin; shortness of breath, wheezing or difficulty in breathing; swelling of the face, lips, tongue or other parts of the body.

If you are not sure if you have or have had an allergic reaction to METHYLPRED, check with your doctor,

You must not be given this medicine if you have a current serious or uncontrolled fungal infection. Your doctor will advise you whether use of METHYLPRED is appropriate in those particular circumstances.

Tell your doctor if you have recently been vaccinated or immunised. METHYLPRED must not be used with certain types of vaccines.

Your doctor will advise whether use of METHYLPRED is appropriate in those particular circumstances.

Do not administer this medicine to yourself.

METHYLPRED must be administered by intravenous or intramuscular injection.

It should not be administered in the spinal cord (intrathecal or epidural) or by local injection due to the risk of serious side effects.

You must not be given this medicine after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering.

If you are not sure whether you should be given this medicine, talk to your doctor.

Before you are given METHYLPRED

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you have or have had any of the following medical conditions:

any infections
unusually high stress due to trauma or infection
stomach ulcers
diseases of the bowel such as ulcerative colitis
thin or weak bones, or bones that tend to break easily (osteoporosis)
diabetes or increased sugar in your blood
disease of the heart e.g., high blood pressure (hypertension) or congestive heart failure
kidney or liver disease
underactive thyroid gland
condition or tumour of the adrenal and/or pituitary glands
mental disorder
myasthenia gravis (ongoing chronic fatigue and muscle weakness)
tuberculosis (TB)
herpes simplex of the eye
recent head injuries
fits or convulsions
Blood clots
Systemic sclerosis

Tell your doctor that you are being treated with METHYLPRED if you are scheduled to have any laboratory tests (e.g. blood or urine).

The use of METHYLPRED may disguise the signs of infections due to a decrease in the body's response to the infection.

Tell your doctor if you are pregnant or plan to become pregnant or are breast-feeding. Your doctor can discuss with you the benefits and possible risks of being given this medicine during pregnancy or breastfeeding.

If you have not told your doctor about any of the above, tell them before you start being given METHYLPRED.

Children

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

Some of the METHYLPRED products contain benzyl alcohol once reconstituted. Benzyl alcohol has been associated with rare but serious side effects in infants. Your doctor will decide if treatment is appropriate.

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.

Taking other medicines

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

Some medicines and METHYLPRED may interfere with each other. These include:

non-steroidal anti-inflammatory medicines such as salicylates or aspirin, medicines used to relieve pain, swelling and other symptoms of inflammation including arthritis
bronchodilators e.g. salbutamol
medicines used to treat TB e.g. isoniazid
neuromuscular blocking drugs, e.g. pancuronium, vercuronium
some antibiotics e.g. erythromycin, rifamipicin
some antifungal agents e.g. ketoconazole, amphotericin B (amphotericin)
medicines used to treat HIV e.g. indinavir, ritonavir
blood pressure, heart disease or stroke medicines e.g. digoxin, diltiazem
some diuretics e.g. furosemide (frusemide)
medicine for nausea, e.g. aprepitant, fosaprepitant
oral contraceptives
anticonvulsants e.g. phenobarbital (phenobarbitone), phenytoin
anticoagulants e.g. heparin, warfarin
antidiabetic medicines e.g. insulin, glibenclamide, metformin
immunosuppressants e.g. methotrexate, ciclosporin
some immunisations, inoculations or vaccinations
medicines to treat anxiety and psychiatric disorders
medications for myasthenia gravis
certain medicines to treat breast cancer
grapefruit juice

These medicines may be affected by METHYLPRED or may affect how well it works. You may need different amounts of your medicines or you may need to take different medicines.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while being treated with this medicine.

How it is given

How much is given

Your doctor will decide what dose you will receive. This depends on the condition being treated and your response to the treatment. Your doctor may change the dose and frequency of your medicine as your condition changes.

How it is given

METHYLPRED is a sterile powder which is dissolved and diluted with suitable sterile fluids.

It is given by direct injection either into a vein or muscle or less frequently via an intravenous (I.V. line) line.

It must not be given intrathecally, epidurally or by local injection due to the risk of serious side effects.

Do not administer this medicine to yourself. Your doctor or nurse will prepare METHYLPRED for you.

If you are given too much (overdose)

As METHYLPRED is given to you under the supervision of your doctor, it is extremely unlikely that you will be given too much.

However, if you experience any side effects after being given METHYLPRED, tell your doctor or nurse immediately. Ask your doctor or pharmacist if you have any concerns.

Repeated frequent doses over a long period of time may cause an increase in side effects.

Immediately telephone your doctor or Poisons Information Centre on 13 11 26 for advice, or go to Accident and Emergency (Casualty) at your nearest hospital if you think your doctor may have been given too much METHYLPRED.

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.

While being treated with METHYLPRED

Things you must do

Tell your doctor immediately if you notice any unusual symptoms.

If you are about to start taking any new medicines, tell your doctor or pharmacist that you are being treated with METHYLPRED.

Tell any doctor, dentist or pharmacist who treats you that you are being treated with METHYLPRED.

Tell your doctor immediately if you become pregnant while taking METHYLPRED.

If you are about to have any blood test, tell you doctor that you are taking METHYLPRED. It may interfere with some of the results.

Keep all your doctor's appointments so that your progress can be checked.

Things to be careful of

Avoid drinking grapefruit juice while you are being treated with METHYLPRED. Grapefruit may interact with METHYLPRED and affect the way your body uses the medicine.

Be careful when driving or operating machinery until you know how METHYLPRED affects you. METHYLPRED may cause dizziness, light headedness, visual disturbances, and fatigue in some patients.

Do not drive or operate machinery or do anything else that could be dangerous, if you have any of these symptoms.

Side effects

Tell your doctor or nurse as soon as possible if you do not feel well while you are being treated with METHYLPRED.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

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

Tell your doctor, nurse or pharmacist if you notice any of the following and they worry you:

weight gain as a result of fluid retention or increased appetite
muscle weakness or loss of muscle mass
loss of ability to feel pain in the joint and instability of the joint
pain when putting weight or pressure on a joint
increased sweating
headache or dizziness
light headedness
fatigue or generally feeling unwell
changes in your menstrual periods
mood changes
mental abnormalities such as memory loss, reduced perception and problem solving skills
nausea and vomiting
itchy or peeling skin
loss of appetite or weight loss
thin fragile skin or bruising
facial redness or bands, stripes or lines on the skin
acne
excessive hair growth particularly in women
lumps as a result of fat deposits in the tissues
stomach pain or discomfort
diarrhoea
pain or redness at the injection site
persistent hiccups

The above list includes the more common side effects of your medicine. They are usually mild and short-lived.

Tell your doctor immediately if you notice any of the following:

bone weakness possibly leading to fractures
wounds that will not heal
red, purple or brown patches on your skin
yellowing of the skin or eyes, dark urine, loss of appetite
loss of sensation or problems with your reflexes (slow or too fast)
deterioration in the control of diabetes mellitus.

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
signs of frequent infections such as fever, severe chills, sore throat or mouth ulcers
allergic-type reactions e.g. skin rash, itching and difficulty breathing, wheezing or coughing (anaphylactic reactions)
swelling or hands, ankles or feet
swelling of the face, lips, mouth, tongue or throat which may cause difficulty in swallowing or breathing
difficulty or pain when swallowing, heartburn or inflammation of food pipe
poor appetite, fever, chills, nausea and a persistent stomach ache that becomes worse with movement
uncomfortable or severe stomach pains or belching after eating
convulsions or fits
vision changes such as blurred vision or loss of vision, distorted vision or a blind spot in your central vision, pressure in the eye
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.

These side effects are serious and may need urgent medical attention.

Long term treatment with corticosteroids such as METHYLPRED may also cause:

chemical imbalances in the blood and urine
swelling of the pancreas (pancreatitis)
bleeding in the stomach
masking of infections
increased risk of infection
hormone changes
metabolic changes
changes in liver enzymes
increased blood pressure
increased number of white blood cells (leucocytosis)
cataracts and other eye diseases.

Tell your doctor if you notice anything else that is making you feel unwell, even if you think the problems are not connected with this medicine and are not referred to in this leaflet.

This is not a complete list of all possible side-effects. Other side effects not listed above may also occur in some people.

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

After using it

Storage

Normally your doctor will get METHYLPRED from the hospital pharmacy or their consulting rooms. If you take your METHYLPRED from the pharmacy to your doctor, it is important to store it in a safe place, away from heat and light, where the temperature stays below 25°C.

Keep it where young children cannot reach it. If for any reason you take your METHYLPRED home, always ensure that it is stored in a place where children cannot reach it.

Do not leave METHYLPRED in a car.

Disposal

If your doctor stops treating you with METHYLPRED, your hospital pharmacist will dispose of any unused medicine.

The expiry date is printed on the labels. METHYLPRED should not be used after this date has passed.

Product description

What it looks like

METHYLPRED is available in four strengths:

40 mg
125 mg
500 mg
1000 mg

All strengths are a white to off white powder in a vial. The powder is dissolved and diluted with suitable sterile fluids before it is used.

Available in the following pack sizes:

40 mg: packs of 5 vials
125 mg: packs of 1 vial
500 mg: packs of 1 vial
1000 mg: packs of 1 vial.

Ingredients

Active ingredients:

Each vial contains either 40 mg, 125 mg, 500 mg or 1.0 g of methylprednisolone (as methylprednisolone sodium succinate).

Inactive ingredients:

dibasic sodium phosphate
monobasic sodium phosphate dihydrate
lactose monohydrate (40 mg only)

Sponsor

METHYLPRED is supplied in Australia by:

Alphapharm Pty Limited
Level 1, 30 The Bond
30-34 Hickson Road
Millers Point NSW 2000
www.mylan.com.au

Australian Registration Numbers:

40 mg: AUST R 145028

125 mg: AUST R 145102

500 mg: AUST R 145103

1000 mg: AUST R 161750.

This leaflet was prepared on
27 August 2019.

Methylpred_cmi\Aug19/00

Published by MIMS October 2019

BRAND INFORMATION

Brand name

Methylpred

Active ingredient

Methylprednisolone sodium succinate

Schedule

1 Name of Medicine

Methylprednisolone sodium succinate.

2 Qualitative and Quantitative Composition

Methylpred powder for injection contains 40 mg, 125 mg, 500 mg or 1.0 g methylprednisolone (as methylprednisolone sodium succinate) as the active ingredient.

List of excipients with known effect.

Lactose (40 mg strength only).
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Methylpred is a white to off white lyophilised plug or powder.

4 Clinical Particulars

4.1 Therapeutic Indications

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 following conditions.
For intravenous or intramuscular use only.

Endocrine disorders.

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

Rheumatic disorders.

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

Collagen disease.

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

Dermatological diseases.

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

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, serum sickness, seasonal or perennial allergic rhinitis, acute noninfectious laryngeal oedema [adrenaline (epinephrine) is the drug of first choice].

Ophthalmic diseases.

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

Gastrointestinal diseases.

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

Respiratory diseases.

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

Haematologic disorders.

Idiopathic thrombocytopenic purpura in adults (intravenous only, intramuscular administration is contraindicated), secondary thrombocytopenia in adults, acquired (autoimmune) haemolytic anaemia, erythroblastopenia (red blood cell anaemia), congenital (erythroid) hypoplastic anaemia.

Neoplastic diseases.

For palliative management of leukaemias and lymphomas in adults, 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 neurological or myocardial involvement.
Methylpred is beneficial as adjunctive therapy in the treatment of acquired immune deficiency syndrome (AIDS) affected patients with moderate to severe Pneumocystis jiroveci pneumonia when given within the first 72 hours of initial antipneumocystis treatment.

4.2 Dose and Method of Administration

A needle with 21G [0.8 mm] diameter size is advised to be used for reconstitution. When inserting syringe into the vial, via the rubber stopper, it is recommended to slice the bung with the bevelled edge facing upwards.
Methylpred may be administered by intravenous or intramuscular injection or by intravenous infusion, the preferred method for initial emergency use being intravenous injection. To administer by intravenous (or intramuscular) injection, prepare solution as directed. The desired dose, if 250 mg or less, may be administered intravenously over at least five minutes. Intramuscular injections (250 mg or less) should be injected slowly into a large muscle. If desired, the medication may be administered in diluted solutions by adding water for injections and withdrawing the indicated dose.
When high dose therapy is desired (i.e. greater than 250 mg), the recommended dose of Methylpred sterile powder is 30 mg/kg administered intravenously over at least 30 minutes (see Section 4.4 Special Warnings and Precautions for Use; Section 4.8 Adverse Effects (Undesirable Effects); Section 4.9 Overdose). This dose may be repeated every four to six hours for up to 48 hours.
In general, high dose corticosteroid therapy should be continued only until the patient's condition has stabilised; usually not beyond 48 to 72 hours.
Although the adverse effects associated with high dose short-term corticoid therapy are uncommon, peptic ulceration may occur. Prophylactic antacid therapy may be indicated.
For other indications, initial dosage will vary from methylprednisolone 10 to 500 mg depending on the clinical problem being treated. The larger doses may be required for short-term management of severe, acute conditions. The initial dose, up to 250 mg, should be given intravenously over a period of at least five minutes, and if greater than 250 mg, then over at least 30 minutes. Subsequent doses may be given intravenously or intramuscularly at intervals dictated by the patient's response and clinical condition. Corticoid therapy is an adjunct to, and not replacement for, conventional therapy.
Dosage may be reduced for infants but should be governed more by the severity of the condition and response of the patient than by age or size. It should not be less than 0.5 mg/kg every 24 hours.

Warning.

Benzyl alcohol has been reported to be associated with a fatal "gasping syndrome" in premature infants (see Section 4.4 Special Warnings and Precautions for Use, Paediatric use).
Dosage must be decreased or discontinued gradually when the drug has been administered for more than a few days. 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 glucose, determination of blood pressure and bodyweight, and a chest X-ray should be made at regular intervals during prolonged therapy. The state of the upper gastrointestinal tract should be monitored in patients with a history of ulceration or significant dyspepsia.

Pneumocystis jiroveci pneumonia.

For patients diagnosed with Pneumocystis jiroveci pneumonia (PCP), presenting with a PaO₂ (arterial oxygen pressure) under 55 mmHg on room air, or where respiratory failure is considered likely, the following regimen should be administered.
Administer Methylpred powder for injection 40 mg intravenously every six hours for five to seven days. Upon improvement, oral prednisolone should be instituted with the following tapering regimen: 60 mg (divided four times daily) for two days; 50 mg (divided twice daily) for two days; 40 mg (divided twice daily) for two days; 30 mg (divided twice daily) for two days; 20 mg (divided twice daily) for two days; 15 mg (divided twice daily) for two days; 10 mg (divided twice daily) for two days; 5 mg (divided twice daily) for two days, then cease.
Treatment with prednisolone should last a maximum of 21 days or until the end of antipneumocystis therapy.
The following four clinical points should be considered when using adjunctive corticosteroid therapy for AIDS related PCP.
1. Adjunctive corticosteroid therapy should be initiated early (within 72 hours of starting antipneumocystis therapy).
2. The diagnosis of PCP must be confirmed and other pulmonary pathogens ruled out because of the potential for masking symptoms of untreated infections.
3. Antimycobacterial therapy should be initiated along with antipneumocystis therapy in patients with a current positive PPD test or in other high risk patients.
4. Adjunctive corticosteroid therapy should be commenced with the maximum recommended dose. The duration of treatment at this dose should be dependent upon both the severity of the disease and the clinical response to therapy. Following a satisfactory clinical response, a tapering regimen should be instituted. The use of a tapering regimen decreases the potential for relapse upon the discontinuation of corticosteroid therapy.

Multiple sclerosis.

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

Recommended administration times.

Intravenous use.

See Table 1.

Intramuscular use.

Intramuscular injections (250 mg or less) should be injected slowly into a large muscle.

Reconstitution of Methylpred.

Methylpred should be reconstituted using bacteriostatic water for injections with benzyl alcohol or sterile water for injections. Parenteral drug products should be inspected visually for particulate matter and discolouration prior to administration whenever solution and container permit.
It is recommended that the reconstituted solution of Methylpred be used immediately upon preparation.
The volume of diluent recommended and the resulting concentration is as follows. See Table 2.

Preparation of solutions for intravenous infusion.

To prepare solutions for intravenous infusion, first prepare the solution for injection as directed above. This solution may then be added to glucose intravenous infusion 5%, sodium chloride intravenous infusion 0.9% or glucose 5% and sodium chloride 0.9% intravenous infusion: the resulting admixtures should be used immediately. This solution is for single use only.

4.3 Contraindications

Methylprednisolone sodium succinate is contraindicated:
in patients who have systemic fungal infections;
in patients with known hypersensitivity to methylprednisolone or any component of the formulation. The 40 mg strength presentation includes lactose produced from cow's milk. This presentation may contain trace amounts of milk ingredients and is therefore contraindicated in patients with a known hypersensitivity to cow's milk or its components, or to other dairy products.
Methylprednisolone sodium succinate is contraindicated for intrathecal, epidural or local injection, or any other unspecified route of administration.
Administration of live or live attenuated vaccines is contraindicated 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 should be gradual. Since complications of treatment with glucocorticoids are dependent on 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.

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, protozoal or helminthic infections, in any location of the body, may be associated with the use of corticosteroids alone or in combination with other immunosuppressive agents that affect cellular immunity, humoral immunity or neutrophil function. These infections may be mild but can be severe and at times fatal. With increasing doses of corticosteroids, the rate of occurrence of infectious complications increases.
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.
Similarly, corticosteroids should be used with great care in patients with known or suspected parasitic infections such as Strongyloides (threadworm) infestation, which may lead to Strongyloides hyperinfection and dissemination with widespread larval migration, often accompanied by severe enterocolitis and potentially fatal Gram negative septicaemia.
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 Methylpred powder for injection 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.
The use of Methylpred in patients with AIDS (as in the adjunctive treatment of Pneumocystis jiroveci pneumonia) may be associated with an increased rate of reactivation of tuberculosis. Consideration should therefore be given to the administration of antimycobacterial therapy if corticosteroids are used in this high risk group. Such patients should also be observed for the activation of other latent infections and judicious examinations of sputum/ bronchoalveolar fluid should be made for the presence of other infectious agents.
Kaposi's sarcoma has been reported to occur in patients receiving corticosteroid therapy. Discontinuation of corticosteroids may result in clinical remission.
A study has failed to establish the efficacy of Methylpred in the treatment of sepsis syndrome and septic shock. Thus, routine use in septic shock is not recommended. The study also suggests that treatment of these conditions with Methylpred may increase the risk of mortality in certain patients (i.e. patients with elevated serum creatinine levels or patients who develop secondary infections after Methylpred).

Immune system effects.

Allergic reactions 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.
In patients receiving the 40 mg presentation of methylprednisolone sodium succinate during the treatment for acute allergic conditions and where these symptoms worsen or any new allergic symptoms occur, consideration should be given to the potential for hypersensitivity reactions to cow's milk ingredients (see Section 4.3 Contraindications). If appropriate, administration of methylprednisolone sodium succinate should be stopped, and the patient's condition should be treated accordingly. Alternative treatments, including the use of corticosteroid formulations that do not contain ingredients produced from cow's milk, should be considered for acute allergy management, where appropriate.

Cardiac effects.

There are reports of cardiac arrhythmias and/or circulatory collapse and/or cardiac arrest following the rapid administration of large doses of intravenous Methylpred (greater than 0.5 g administered over a period of less than ten minutes). Bradycardia has been reported during or after the administration of large doses of methylprednisolone sodium succinate, and may be unrelated to the speed or duration of infusion (see Section 4.2 Dose and Method of Administration; Section 4.8 Adverse Effects (Undesirable Effects); Section 4.9 Overdose).
Adverse effects of glucocorticoids on the cardiovascular system, such as dyslipidaemia and hypertension, may predispose treated patients with existing cardiovascular risk factors to additional cardiovascular effects if high doses and prolonged courses are used. Accordingly, corticosteroids should be employed judiciously in such patients and risk modification and additional cardiac monitoring may need to be considered. Low dose and alternate day therapy may reduce the incidence of complications in corticosteroid therapy.
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 a 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.

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 resolve 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 nonspecific 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).
Severe medical events have been reported in association with the intrathecal/ epidural routes of administration (see Section 4.8 Adverse Effects (Undesirable Effects)).
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 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.

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 nonsteroidal anti-inflammatory agents should be used cautiously in conjunction with corticosteroids (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions, Table 4, NSAIDs).
Benzyl alcohol has been reported to be associated with a fatal "gasping syndrome" in premature infants (see Section 4.4 Special Warnings and Precautions for Use, Musculoskeletal effects, Paediatric use).

Use in hepatic impairment.

Drug-induced liver injury such as acute hepatitis can result from cyclical pulsed IV methylprednisolone (usually at doses of 1 g/day). The time to onset of acute hepatitis can be several weeks or longer. Resolution of the adverse event has been observed after treatment was discontinued. Serious hepatotoxicity has been reported.
There is an enhanced effect of corticosteroids in patients with cirrhosis.

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.

Benzyl alcohol, which can be found in the alternative recommended diluent, is associated with severe adverse effects, including fatal "gasping syndrome", in paediatric patients. The minimum amount of benzyl alcohol at which toxicity may occur is unknown. The risk of benzyl alcohol toxicity depends on the quantity administered and the liver and kidneys' capacity to detoxify the chemical. Premature and low birthweight infants, as well as patients receiving high dosages, may be more likely to develop toxicity. Practitioners administering this and other medications containing benzyl alcohol should consider the combined daily metabolic load of benzyl alcohol from all sources.
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. Alternate day glucocorticoid therapy usually prevents or minimises this side effect.
Infants and children on prolonged corticosteroid therapy are at special risk from raised intracranial pressure.
High doses of corticosteroids may produce pancreatitis in children.

Effects on laboratory tests.

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.

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 in Table 3 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 a 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 methylprednisolone and examples of CYP3A4 inhibitors, inducers and substrates are provided in Table 3 and Table 4. Table 3 and Table 4 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 nonviable fetuses. Other corticosteroids have been shown to impair fertility and reduce embryonic viability in studies in mice and rats.
(Category A)
Corticosteroids have been shown to be teratogenic in many species when given in doses equivalent to the human dose. In animal reproduction studies, glucocorticoids such as methylprednisolone have been shown to increase the incidence of malformations (cleft palate, skeletal malformations), embryofetal lethality (e.g. increase in resorptions), and intrauterine growth retardation and abortions.
There is limited data on the use of methylprednisolone sodium succinate in pregnant women, and animal reproduction studies have not been done. Methylprednisolone sodium succinate should be used in pregnancy only after a careful assessment of the benefit-risk ratio to the mother and fetus.
Some corticosteroids readily cross the placenta. An increased incidence of low birthweights in infants born of mothers receiving corticosteroids has been reported.
Infants exposed in utero to substantial doses of corticosteroids must be carefully observed and evaluated for signs of adrenal insufficiency.
Cataracts have been observed in infants born to mothers treated with long-term corticosteroids during pregnancy.
Benzyl alcohol can cross the placenta (see Section 4.4 Special Warnings and Precautions for Use, Paediatric use).
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 breastfeeding only after a careful assessment of the benefit-risk ratio to the mother and infant.

4.7 Effects on Ability to Drive and Use Machines

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

4.8 Adverse Effects (Undesirable Effects)

Serious undesirable adverse events are also mentioned, see Section 4.4 Special Warnings and Precautions for Use.
The following adverse reactions have been reported with the following contraindicated routes of administration. Intrathecal/ epidural: arachnoiditis, functional gastrointestinal disorder/ bladder dysfunction, headache, meningitis, paraparesis/ paraplegia, seizure, sensory disturbance.
The adverse effects are listed below by system organ class.

Infections and infestations.

Opportunistic infection, infection^a, peritonitis^g.

Blood and lymphatic system disorders.

Leucocytosis.

Immune system disorders.

Drug hypersensitivity^b, anaphylactic reaction, anaphylactoid reaction.

Endocrine disorders.

Cushingoid, hypopituitarism, steroid withdrawal syndrome, adrenal insufficiency, secondary adrenocortical and pituitary unresponsiveness^c.

Metabolism and nutrition disorders.

Metabolic acidosis, sodium retention, fluid retention, alkalosis hypokalaemic, dyslipidaemia, glucose tolerance impaired^d, increased insulin requirement (or oral hypoglycaemic agents in diabetics), lipomatosis, increased appetite (which may result in weight increased).

Psychiatric disorders.

Affective disorder (including depressed mood, euphoric mood, affect lability, drug dependence, suicidal ideation), psychotic disorder (including mania, delusion, hallucination and schizophrenia), mental disorder, personality change, confusional state, anxiety, mood swings, abnormal behaviour, insomnia, irritability.

Nervous system disorders.

Epidural lipomatosis, intracranial pressure increased (with papilloedema [benign intracranial hypertension]), seizure, amnesia, cognitive disorder, dizziness, headache.

Eye disorders.

Chorioretinopathy, cataract, glaucoma, exophthalmos, vision blurred.

Ear and labyrinth disorders.

Vertigo.

Cardiac disorders.

Cardiac failure congestive (in susceptible patients), myocardial rupture^e, arrhythmia.

Vascular disorders.

Thrombosis, hypertension, hypotension.

Respiratory, thoracic, and mediastinal disorders.

Pulmonary embolism, hiccups.

Gastrointestinal disorders.

Peptic ulcer (with possible peptic ulcer perforation and peptic ulcer haemorrhage), intestinal perforation, gastric haemorrhage, pancreatitis, oesophagitis ulcerative, oesophagitis, vomiting, abdominal distension, abdominal pain, diarrhoea, dyspepsia, nausea.

Hepatobiliary disorders.

Hepatitis^f.

Skin and subcutaneous tissue disorders.

Angioedema, hirsutism, petechiae, ecchymosis, subcutaneous atrophy, skin atrophy, erythema, hyperhidrosis, skin striae, rash, pruritus, urticaria, acne, skin hyperpigmentation, skin hypopigmentation.

Musculoskeletal and connective tissue disorders.

Muscular weakness, myalgia, myopathy, muscle atrophy, osteoporosis, osteonecrosis, pathological fracture, neuropathic arthropathy, arthralgia, growth retardation.

Reproductive system and breast disorders.

Menstruation irregular.

General disorders and administration site conditions.

Abscess sterile, impaired healing, oedema peripheral, fatigue, malaise, injection site reaction.

Investigations.

Intraocular pressure increased, carbohydrate tolerance decreased, blood potassium decreased, urine calcium increased, alanine aminotransferase increased, aspartate aminotransferase increased, blood alkaline phosphatase increased, blood urea increased, suppression of reactions to skin tests^h.

Injury, poisoning and procedural complications.

Spinal compression fracture, tendon rupture.
^a Including masking of infections and latent infections becoming active.
^b With or without circulatory collapse, cardiac arrest, bronchospasm, or hypertension.
^c Particularly in times of stress, as in trauma, surgery or illness.
^d Manifestations of latent diabetes mellitus.
^e Following a myocardial infarction.
^f Hepatitis has been reported with IV administration (see Section 4.4 Special Warnings and Precautions for Use).
^g Peritonitis may be the primary presenting sign or symptom of a gastrointestinal disorder such as perforation, obstruction or pancreatitis (see Section 4.4 Special Warnings and Precautions for Use).
^h Not a MedDRA preferred term.

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.

4.9 Overdose

Symptoms.

Reports of acute toxicity and metabolic disturbances with glucocorticoids are rare but do occur. There is no clinical syndrome of acute overdosage with Methylpred powder for injection. Acute overdose may possibly aggravate pre-existing disease states, e.g. 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.

Treatment.

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.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Methylprednisolone is a potent anti-inflammatory steroid. It has a greater anti-inflammatory potency than prednisolone and even less tendency than prednisolone to induce sodium and water retention.

Mechanism of action.

Methylprednisolone sodium succinate has the same metabolic and anti-inflammatory actions as methylprednisolone. When given parenterally and in equimolar quantities, the two compounds are equivalent in biological activity. The relative potency of Methylpred powder for injection and hydrocortisone sodium succinate, as indicated by depression of eosinophil count following intravenous administration, is at least four to one. This is in good agreement with the relative oral potency of methylprednisolone and hydrocortisone.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Peak methylprednisolone plasma levels of approximately 20 microgram/mL are reached after intravenous infusions of 30 mg/kg bodyweight administered over 20 minutes, or 1 g over 30 to 60 minutes, while levels of 42 to 47 microgram/mL are measured after an intravenous bolus injection of 40 mg. Peak methylprednisolone plasma levels of 34 microgram/100 mL are measured after 120 minutes following a 40 mg intramuscular injection. Lower peak methylprednisolone plasma levels are achieved following intramuscular injection than following intravenous administration. However, the peak plasma value persists for a longer period following intramuscular administration resulting in equivalent quantities of methylprednisolone reaching the plasma independent of the route of administration.
The plasma half-life of methylprednisolone is 2.3 to 4 hours and appears to be independent of the route/ pattern of administration. The biological half-life is 12 to 38 hours. The intracellular activity of glucocorticoids results in the marked variation in the plasma and pharmacological half-lives. Pharmacological activity persists after plasma levels are no longer measurable.
The duration of the anti-inflammatory action of glucocorticoids approximately equals the duration of the hypothalamic pituitary adrenal (HPA) axis suppression.

Metabolism.

In vivo, cholinesterases rapidly hydrolyse methylprednisolone sodium succinate to free methylprednisolone. In humans, methylprednisolone forms a weak dissociable bond with albumin and transcortin; approximately 40 to 90% of the drug is bound.
Metabolism of methylprednisolone occurs via the hepatic route and is qualitatively similar to metabolism of cortisol. The major metabolites are 20-beta-hydroxymethylprednisolone and 20-beta-hydroxy-6-alpha-methylprednisolone.

Excretion.

The metabolites are mainly excreted in the urine as glucuronides, sulfates and unconjugated compounds. Following intravenous administration of 14C-labelled methylprednisolone, 75% of the total radioactivity was recovered in the urine in 96 hours, 9% in faeces after five days and 20% in the bile.

5.3 Preclinical Safety Data

Genotoxicity.

Methylprednisolone sodium succinate has not been formally evaluated for genotoxicity. However, methylprednisolone sulfonate, which is structurally similar to methylprednisolone sodium succinate, 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.

6 Pharmaceutical Particulars

6.1 List of Excipients

The excipients include dibasic sodium phosphate, monobasic sodium phosphate dihydrate and lactose monohydrate (for the 40 mg strength only).

6.2 Incompatibilities

To avoid compatibility and stability problems, whenever possible it is recommended that Methylpred be administered separately from other drugs and as either an intravenous injection through an intravenous medication chamber, microburette or as an intravenous 'piggy-back' solution. The intravenous compatibility and stability of methylprednisolone sodium succinate, either alone in solution or in admixtures with other drugs, is dependent on pH, concentration, time, temperature and the ability of methylprednisolone to solubilise itself.
Drugs that are physically incompatible in solution with methylprednisolone sodium succinate include, but are not limited to: allopurinol sodium, doxapram hydrochloride, tigecycline, diltiazem hydrochloride, calcium gluconate, vecuronium bromide, rocuronium bromide, cisatracurium besilate, glycopyrronium bromide (glycopyrrolate), propofol.

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

Store below 25°C. Protect from light.
When reconstituted using bacteriostatic water for injections with benzyl alcohol, or sterile water for injections, the resulting solution should be used immediately. Discard any unused portion.

6.5 Nature and Contents of Container

Container types: Type 1 clear glass vials.
Pack sizes: 1, 5.
Not all strengths, pack sizes and/or types may be available.

6.6 Special Precautions for Disposal

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

6.7 Physicochemical Properties

Chemical structure.

Sodium 4-[(11β,17-dihydroxy-6α-methyl-3,20-dioxopregna-1,4-dien-21-yl) oxy]-4-oxobutanoate.
Molecular formula: C₂₆H₃₃NaO₈.
Molecular weight: 496.53.
Methylprednisolone sodium succinate is a white or nearly white, odourless, hygroscopic, amorphous solid.
It is very soluble in water and in alcohol; it is insoluble in chloroform and is very slightly soluble in acetone. Its melting point is greater than 250°C.
Methylprednisolone sodium succinate is extremely soluble in water so that it may be administered in a small volume of diluent and is especially well suited for intravenous use in situations in which high blood levels of methylprednisolone are required rapidly.

CAS number.

2375-03-3.

7 Medicine Schedule (Poisons Standard)

S4 (Prescription Only Medicine).

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Methylprednisolone sodium succinate

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