Consumer medicine information

Solu-Medrol

Methylprednisolone sodium succinate

BRAND INFORMATION

Brand name

Solu-Medrol

Active ingredient

Methylprednisolone sodium succinate

Schedule

S4

 

Consumer medicine information (CMI) leaflet

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

SUMMARY CMI

SOLU-MEDROL®

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I given SOLU-MEDROL?

SOLU-MEDROL contains the active ingredient methylprednisolone sodium succinate. SOLU-MEDROL is used for treatment of various medical conditions including skin diseases, allergic reactions, inflammation of the eyes, respiratory diseases and certain respiratory infections, diseases of the gut, multiple sclerosis, rheumatic disorders, diseases of the blood and treatment of certain glandular conditions. For more information, see Section 1. Why am I given SOLU-MEDROL? in the full CMI.

2. What should I know before I receive SOLU-MEDROL?

Do not use if you have ever had an allergic reaction to methylprednisolone sodium succinate or any of the ingredients listed at the end of the CMI. Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.
For more information, see Section 2. What should I know before I receive SOLU-MEDROL? in the full CMI.

3. What if I am taking other medicines?

Some medicines and food may interfere with SOLU-MEDROL and affect how it works. Tell your doctor if you are taking any other medicines including medicines used to relieve pain or swelling, some antibiotics, oral contraceptives, anticoagulants, anticonvulsants and antidiabetic medicines.
A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How is SOLU-MEDROL given?

This medicine will be administered under medical supervision. SOLU-MEDROL must be administered by intravenous or intramuscular injection. You must not administer this medicine to yourself.
The dose, how often and how long you are treated with SOLU-MEDROL will depend on your medical condition and also on your weight. Your doctor may change the dose and how many times a day you have it, as your condition changes.
More instructions can be found in Section 4. How is SOLU-MEDROL given? in the full CMI.

5. What should I know while on SOLU-MEDROL?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are being treated with SOLU-MEDROL.
  • Tell your doctor immediately if you notice any unusual symptoms.
Things you should not do
  • Avoid drinking grapefruit juice while you are being treated with SOLU-MEDROL.
Driving or using machines
  • Be careful when driving or operating machinery until you know how SOLU-MEDROL affects you.
  • It may cause dizziness, light headedness, visual disturbances, and fatigue in some patients
Looking after your medicine
  • Normally your doctor will get SOLU-MEDROL from the hospital pharmacy or their consulting rooms.
  • Store it in a safe place away from heat (below 25°C).

For more information, see Section 5. What should I know while on SOLU-MEDROL? in the full CMI.

6. Are there any side effects?

All medicines can have side effects and SOLU-MEDROL may have unwanted side effects in a few people. Some of the common side effects are weight gain/loss, increased/decreased appetite, muscle weakness or loss of muscle mass, increased sweating, headache/dizziness, light headedness, fatigue, nausea, vomiting, itchy/peeling/thin fragile skin, acne and stomach pain/ discomfort or diarrhoea. If you experience side effects such as bone weakness/fracture, wounds not healing or red/purple/brown patches of skin, yellowing of the skin/eyes, dark urine, you should tell your doctor immediately. If you experience severe headache or stomach pain, blurred/double vision, convulsions or fits, chest pain or any allergic-type reactions such as skin rash, itching and difficulty breathing, tell your doctor immediately or go to Accident and Emergency at your nearest hospital.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

SOLU-MEDROL®

Active ingredient(s): Methylprednisolone sodium succinate


Consumer Medicine Information (CMI)

This leaflet provides important information about using SOLU-MEDROL. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using SOLU-MEDROL.

Where to find information in this leaflet:

1. Why am I given SOLU-MEDROL?
2. What should I know before I receive SOLU-MEDROL?
3. What if I am taking other medicines?
4. How is SOLU-MEDROL given?
5. What should I know while on SOLU-MEDROL?
6. Are there any side effects?
7. Product details

1. Why am I given SOLU-MEDROL?

SOLU-MEDROL contains the active ingredient methylprednisolone sodium succinate.

SOLU-MEDROL belongs to a group of medicine called corticosteroids. SOLU-MEDROL acts in the body by reducing 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.

SOLU-MEDROL is used to treat of one or more of the following:

  • 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.

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

There is no evidence that SOLU-MEDROL is addictive.

2. What should I know before I receive SOLU-MEDROL?

Warnings

Do not use SOLU-MEDROL if:

  1. you are allergic to methylprednisolone sodium succinate or any of the ingredients listed at the end of this leaflet. The SOLU-MEDROL 40 mg product contains lactose from cow's milk.
  2. Always check the ingredients to make sure you can use this medicine.
  3. you have a severe fungal infection.

Check with your doctor if you:

  • have or have had any of the following medical conditions:
    - disease of the heart, e.g., high blood pressure (hypertension) or congestive heart failure
    - condition or tumour of the adrenal and/or pituitary glands
    - stomach ulcers
    - thin or weak bones, or bones that tend to break easily (osteoporosis)
    - kidney or liver disease
    - underactive thyroid gland
    - emotional and mental disorder
    - myasthenia gravis (ongoing chronic fatigue and muscle weakness)
    - tuberculosis (TB)
    - herpes simplex of the eye
    - any pus producing infections
    - disease of the bowel, e.g., ulcerative colitis or diverticulitis
    - recent head injuries
    - fits or convulsions
    - diabetes or increased sugar in your blood
    - blood clots.
    If you are scheduled to have any laboratory tests, e.g., blood or urine, tell your doctor that you are being treated with SOLU-MEDROL.
    The use of SOLU-MEDROL may disguise the signs of infections due to a decrease in the body's response to the infection. If you are in any doubt please consult your doctor.
  • take any medicines for any other condition
  • have recently been vaccinated or immunised. SOLU-MEDROL must not be used with certain types of vaccines
  • are allergic to any other medicines or any other substances such as foods, preservatives or dyes, especially cow's milk or any other dairy products.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

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 SOLU-MEDROL.

Some of the SOLU-MEDROL products contain benzyl alcohol. Benzyl alcohol has been associated with a rare but serious side effect 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.

If you have not told your doctor about any of the above, tell them before you start treatment with SOLU-MEDROL.

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

Your doctor can discuss with you the risks and benefits involved.

3. What if I am taking other medicines?

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

Some medicines and food may interfere with SOLU-MEDROL and affect how it works. These include:

  • nonsteroidal anti-inflammatory such as salicylates or aspirin, medicines used to relieve pain, swelling and other symptoms of inflammation including arthritis.
  • neuromuscular blocking drugs, e.g., pancuronium
  • some antibiotics, e.g., erythromycin
  • medicines used to treat TB, e.g. isoniazid
  • some anti-fungal agents, e.g., ketoconazole, amphotericin
  • medicines to treat HIV, e.g., indinavir, ritonavir
  • some medicines to treat blood pressure, heart conditions and stroke, e.g., digoxin and diltiazem
  • some diuretics e.g., frusemide, a medicine to help kidneys get rid of salt and water by increasing the amount of urine produced
  • medicine for nausea, e.g., aprepitant, fosaprepitant
  • oral contraceptives
  • medicines used for myasthenia gravis, glaucoma, Alzheimer's disease
  • medicines for psychiatric disorders
  • medicines 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 to treat breast cancer or hormone disorder
  • anticonvulsants e.g., phenytoin, phenobarbitone
  • anticoagulants e.g., heparin, warfarin
  • antidiabetic medicines e.g., insulin, glibenclamide and metformin
  • immunosuppressants e.g., methotrexate and ciclosporin (a medicine used in kidney transplant patients)
  • some immunisations, inoculations or vaccinations
  • grapefruit juice.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect SOLU-MEDROL.

4. How is SOLU-MEDROL given?

This medicine will be administered under medical supervision.

SOLU-MEDROL must be administered by intravenous or intramuscular injection. It must not be given in the spinal cord (intrathecal or epidural) or by local injection due to the risk of serious side effects.

You must not administer this medicine to yourself.

SOLU-MEDROL powder is reconstituted with the diluent provided or Sterile Water for Injections by your doctor or pharmacist.

How much you should be given

The dose and how often you are treated with SOLU-MEDROL will depend on your medical condition and also on your weight. Your doctor may change the dose and how many times a day you have it, as your condition changes.

Your doctor will continue giving you SOLU-MEDROL for as long as your condition requires.

If you are given too much SOLU-MEDROL

SOLU-MEDROL will be administered under medical supervision, so an overdose is unlikely.

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

If you think that you have been given too much SOLU-MEDROL, you may need urgent medical attention.

You should immediately:

  • contact your doctor, or
  • phone the Poisons Information Centre
    (by calling 13 11 26), or
  • go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

Keep the telephone numbers for these services handy.

5. What should I know while on SOLU-MEDROL?

Things you should 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 SOLU-MEDROL.

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

Tell your doctor immediately if you become pregnant while taking SOLU-MEDROL.

If you are about to have any blood test, tell you doctor that you are taking SOLU-MEDROL.

It may interfere with some of the results.

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

Things you should not do

Avoid drinking grapefruit juice while you are being treated with SOLU-MEDROL.

Grapefruit may interact with SOLU-MEDROL and affect the way your body uses the medicine.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how SOLU-MEDROL affects you.

SOLU-MEDROL 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.

Looking after your medicine

Normally your doctor will get SOLU-MEDROL from the hospital pharmacy or their consulting rooms. If you do take your SOLU-MEDROL from the pharmacy to your doctor, it is important to store it in a safe place away from heat (below 25°C).

Do not leave SOLU-MEDROL in a car.

If for any reason you take your SOLU-MEDROL home, always ensure that it is stored in a place where children cannot reach it.

Getting rid of any unwanted medicine

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

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

6. Are there any side effects?

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are being treated with SOLU-MEDROL.

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

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

Common side effects

Common side effectsWhat to do
  • 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
  • changes in your menstrual periods
  • mood changes and other mental disorders such as memory loss, reduced perception and problem-solving abilities
  • nausea
  • vomiting
  • itchy or peeling skin
  • loss of appetite or weight loss
  • thin fragile skin or bruising
  • acne
  • facial redness or bands, stripes or lines on the skin
  • excessive hairiness, particularly in women
  • benign tumour-like lumps as a result of fat deposits in the tissues
  • persistent hiccups
  • stomach pain or discomfort
  • diarrhoea
  • fatigue or generally feeling unwell
  • pain, redness at the injection site.
Speak to your doctor if you have any of these common side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
Call your doctor immediately:
  • bone weakness possibly leading to fractures
  • wounds that will not heal
  • red, purple or brown patches on your skin
  • loss of sensation or problems with your reflexes (slow or too fast)
  • yellowing of the skin or eyes, dark urine, loss of appetite.
Seek Emergency medical attention:
  • signs of increased pressure in the skull, including drowsiness, vomiting, headache, weakness, numbness and /or eye problems such as double vision
  • convulsions or fits
  • blurred or loss of vision, distorted vision or a blind spot in your central vision, pressure in the eye
  • 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 of hands, ankles or feet
  • swelling of the face, lips, mouth, tongue or throat which may cause difficulty in swallowing or breathing
  • inflammation of the food pipe. You may experience difficulty or pain when swallowing or heartburn
  • poor appetite, fever, chills, nausea and a persistent stomach-ache that becomes worse with movement
  • uncomfortable or severe stomach pains or belching after eating
  • pain and tenderness in the leg, pain on extending the foot, swelling of the lower leg, ankle and foot
  • chest pain and breathlessness
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

SOLU-MEDROL can 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 or increased number of white blood cells (leucocytosis). Some of these side effects can only be found when your doctor does tests from time to time to check on your progress.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

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

What SOLU-MEDROL contains

Active ingredient
(main ingredient)
methylprednisolone sodium succinate
Other ingredients
(inactive ingredients)
40 mg ACT-O-VIAL System
  • monobasic sodium phosphate
  • dibasic sodium phosphate
  • lactose monohydrate
  • sodium hydroxide
  • water for injections (diluent)
125 mg ACT-O-VIAL System
  • monobasic sodium phosphate
  • dibasic sodium phosphate
  • sodium hydroxide
  • water for injections (diluent)
500 mg, 1 g and 2 g Vials with Diluent
  • monobasic sodium phosphate
  • dibasic sodium phosphate
  • sodium hydroxide
  • benzyl alcohol (diluent)
  • water for injections (diluent)
500 mg and 1 g Plain Vials
  • monobasic sodium phosphate
  • dibasic sodium phosphate
  • sodium hydroxide

Do not use this medicine if you are allergic to any of these ingredients.

What SOLU-MEDROL looks like

SOLU-MEDROL powder for injection is a white, or nearly white powder in a vial.

SOLU-MEDROL is supplied as:

  • one vial with separate sections containing the powder and the liquid to dissolve the powder ready for injection (ACT-O-VIAL system), or
  • two vials, one containing the powder and the other containing the liquid to dissolve the powder ready for injection, or
  • plain vials containing only the powder.

Available pack sizes:

40 mg ACT-O-VIAL - 5s pack (AUST R 171991)

125 mg ACT-O-VIAL - 1s pack (AUST R 171992)

500 mg vial with diluent - 1s pack (AUST R 12344)

1 g vial with diluent - 1s pack (AUST R 12340)

2 g vial with diluent - 1s pack (AUST R 12342)

500 mg plain vial - 1s and 5s pack (AUST R 50691)

1 g plain vial - 1s and 5s pack (AUST R 50698)

Not all presentations are available.

Who distributes SOLU-MEDROL

Pfizer Australia Pty Ltd
Sydney NSW
Toll Free Number: 1800 675 229
www.pfizermedinfo.com.au

This leaflet was prepared in December 2021.

Published by MIMS March 2022

BRAND INFORMATION

Brand name

Solu-Medrol

Active ingredient

Methylprednisolone sodium succinate

Schedule

S4

 

1 Name of Medicine

Methylprednisolone sodium succinate.

2 Qualitative and Quantitative Composition

Solu-Medrol is available in several strengths for intravenous (IV) or intramuscular (IM) administration.

40 mg Act-O-Vial system.

Each mL (when mixed) contains methylprednisolone sodium succinate equivalent to 40 mg methylprednisolone.

125 mg Act-O-Vial system.

Each 2 mL (when mixed) contains methylprednisolone sodium succinate equivalent to 125 mg methylprednisolone.

500 mg vial with diluent.

Each 8 mL (when mixed as directed) contains methylprednisolone sodium succinate equivalent to 500 mg methylprednisolone.

1 g vial with diluent.

Each 15.6 mL (when mixed as directed) contains methylprednisolone sodium succinate equivalent to 1 g methylprednisolone.

2 g vial with diluent.

Each 31.2 mL (when mixed as directed) contains methylprednisolone sodium succinate equivalent to 2 g methylprednisolone.

500 mg plain vial.

Each vial contains methylprednisolone sodium succinate equivalent to 500 mg methylprednisolone.

1 g plain vial.

Each vial contains methylprednisolone sodium succinate equivalent to 1 g methylprednisolone.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Solu-Medrol 40 mg and 125 mg Act-O-Vial system.

Powder for injection: white freeze dried cake.
Diluent: clear colourless liquid.

Solu-Medrol 500 mg, 1 g and 2 g vials with diluent.

Powder for injection: white freeze dried cake.
Diluent: clear colourless liquid.

Solu-Medrol 500 mg and 1 g plain vials.

Powder for injection: white freeze dried cake.
When necessary, the pH of each formula was adjusted with sodium hydroxide so that the pH of the reconstituted solution is within the USP specified range of 7 to 8 and the tonicities are, for the 40 mg per mL solution, 0.50 osmolar; for the 125 mg per 2 mL, 500 mg per 8 mL and 1 g per 16 mL solutions, 0.40 osmolar; for the 2 g per 31.2 mL solutions, 0.42 osmolar (Isotonic saline = 0.28 osmolar).

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 condition, Solu-Medrol powder for injection is indicated only for intravenous or intramuscular use in the following conditions:

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; epicondylitis; synovitis of osteoarthritis; acute gouty arthritis; acute nonspecific tenosynovitis; 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; pemphigus; severe psoriasis; severe seborrhoeic dermatitis; exfoliative dermatitis; 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; acute noninfectious laryngeal oedema (adrenaline 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 (IV only; IM administration is contraindicated); secondary thrombocytopenia in adults; acquired (autoimmune) haemolytic anaemia; erythroblastopenia (RBC 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 neurologic or myocardial involvement.
Solu-Medrol is beneficial as adjunctive therapy in the treatment of acquired immunodeficiency syndrome (AIDS) patients with moderate to severe Pneumocystis jiroveci pneumonia (PCP) when given within the first 72 hours of initial antipneumocystis treatment.

4.2 Dose and Method of Administration

Dosage.

Solu-Medrol may be administered by intravenous or intramuscular injection or by intravenous infusion. The preferred method for initial emergency use is 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 5 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 or other suitable diluent (see Method of administration) to the Act-O-Vial and withdrawing the indicated dose.
Methylprednisolone sodium succinate is so extremely soluble in water 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.
Dosage requirements are variable and must be individualised on the basis of the disease under treatment, its severity and the response of the patient over the entire duration of treatment. A risk/benefit decision must be made in each individual case on an ongoing basis.
The lowest possible dose of corticosteroid should be used to control the condition under treatment for the minimum period.
If after long-term therapy the drug is to be stopped, it needs to be withdrawn gradually rather than abruptly (see Section 4.4 Special Warnings and Precautions for Use).
When high dose therapy is desired (i.e. greater than 250 mg), the recommended dose of Solu-Medrol sterile powder is 30 mg/kg administered intravenously over at least 30 minutes (see Section 4.4 Special Warnings and Precautions for Use; Section 4.9 Overdose). This dose may be repeated every 4 to 6 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.
In other indications, initial dosage will vary from 10 to 500 mg intravenously, depending on the clinical condition. Larger doses may be required for short-term management of severe, acute conditions. Initial doses up to 250 mg, should be administered intravenously over a period of at least 5 minutes, while larger doses should be administered over at least 30 minutes. Subsequent doses may be administered 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.

Use in paediatrics.

Dosage may be reduced for infants and children but should be selected based on the severity of the condition and response of the patient rather than on the age or weight of the patient. The paediatric dosage should not be less than 0.5 mg per kg every 24 hours.

Warning.

Benzyl alcohol (as contained in the accompanying diluent for the 500 mg, 1 g and 2 g vials) 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 GI 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 40 mg of Solu-Medrol powder for injection intravenously every six (6) hours for 5 to 7 days. Upon improvement, oral prednisolone should be instituted with the following tapering regimen:
60 mg (divided four times daily) for 2 days;
50 mg (divided twice daily) for 2 days;
40 mg (divided twice daily) for 2 days;
30 mg (divided twice daily) for 2 days;
20 mg (divided twice daily) for 2 days;
15 mg (divided twice daily) for 2 days;
10 mg (divided twice daily) for 2 days;
5 mg (divided twice daily) for 2 days, then cease.
Treatment with prednisolone should last a maximum of 21 days or until the end of antipneumocystis therapy.
The following four (4) 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.

Administer 500 mg/day or 1 g/day for 3 or 5 days as IV pulse dosing over at least 30 minutes (4 mg of methylprednisolone is equivalent to 5 mg of prednisolone).

Summary of dosage and administration recommendations.

1. For intravenous use.

See Table 1.

2. For intramuscular use.

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

Method of administration.

Directions for using the Act-O-Vial system.

1. Tap to ensure that the powder is at base of vial and away from the central stopper.
2. Place the Act-O-Vial on a flat, stable surface and hold with one hand.
3. Press down firmly on the plastic activator with the palm of the other hand to force diluent into the lower compartment.
4. Gently mix the solution by turning the vial upside down a number of times. Do not shake the vial.
5. Remove plastic tab covering centre of stopper.
6. Sterilise top of stopper with an alcohol swab.

Note.

Steps 1-6 must be completed before proceeding.
7. Whilst on a flat surface, insert needle squarely through centre of stopper until tip is just visible.
8. Invert vial to allow the solution to flow into the top compartment and withdraw the dose.

Reconstitution of Solu-Medrol.

Solu-Medrol should be reconstituted with the diluent where this is provided. Where no diluent is provided, the sterile powder 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 Solu-Medrol be used immediately upon preparation.
The volume of diluent recommended and the resulting concentration is as follows (see Table 2):

Important.

Use only the accompanying diluent to reconstitute Solu-Medrol vial with diluent (which is bacteriostatic water for injections with benzyl alcohol) and Solu-Medrol Act-O-Vials (which is sterile water for injections). Bacteriostatic water for injections with benzyl alcohol or sterile water for injections may be used when reconstituting Solu-Medrol plain vials.

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 sodium chloride 0.9% and glucose 5% 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 Act-O-Vial 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 or suspected hypersensitivity to cow's milk or its components, or to other dairy products.
Solu-Medrol (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 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.

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 organisms, in any location in the body, may be associated with the use of corticosteroids alone or in combination with other immunosuppressive agents that affect cellular immunity, humoral immunity, or neutrophil function. These infections may be mild, but can be severe and at times fatal. With increasing doses of corticosteroids, the rate of occurrence of infectious complications increases.
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 Solu-Medrol 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 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.
The use of Solu-Medrol 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 Solu-Medrol 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 Solu-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 Solu-Medrol).

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 IV doses of Solu-Medrol (greater than 0.5 g administered over a period of less than 10 minutes). Bradycardia has been reported during or after the administration of large doses of methylprednisolone sodium succinate, and may be unrelated to the speed 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 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 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 non-steroidal anti-inflammatory drugs (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).
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 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.

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, Table 4, NSAIDs).
Benzyl alcohol is contained in the accompanying diluent for the 500 mg, 1 g and 2 g vials. 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). The 40 mg Act-O-Vials and the 125 mg Act-O-Vials do not contain benzyl alcohol.

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 is contained in the accompanying diluent for the 500 mg, 1 g and 2 g vials. The 40 mg Act-O-Vials and the 125 mg Act-O-Vials do not contain benzyl alcohol. Benzyl alcohol 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-birth-weight 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 avoids 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.
Hypertrophic cardiomyopathy may develop after administration of methylprednisolone to prematurely born infants, therefore, appropriate diagnostic evaluation and monitoring of cardiac function and structure should be performed.

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 summarised 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 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 Solu-Medrol and examples of CYP3A4 inhibitors, inducers and substrates are provided in Tables 3 and 4. Tables 3 and 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 non-viable 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, 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 sodium succinate in human pregnancies, 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-birth weights 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 breast feeding 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 (see Section 4.8 Adverse Effects (Undesirable Effects)). If affected, patients should not drive or operate machinery.

4.8 Adverse Effects (Undesirable Effects)

Serious undesirable adverse events are also mentioned under the 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 in Table 5 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.

4.9 Overdose

Reports of acute toxicity and metabolic disturbances with glucocorticoids are rare but do occur. There is no clinical syndrome of acute overdosage with Solu-Medrol powder for injection. 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.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

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.
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 biologic activity. The relative potency of Solu-Medrol 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 IV infusions of 30 mg/kg bodyweight administered over 20 minutes, or 1 g over 30 to 60 minutes, whilst levels of 42-47 microgram/mL are measured after an IV bolus injection of 40 mg. Peak methylprednisolone plasma levels of 34 microgram/100 mL are measured after 120 minutes following a 40 mg intramuscular (IM) injection. Lower peak methylprednisolone plasma levels are achieved following IM injection than IV administration. However, the peak plasma value persists for a longer period following IM 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 36 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 man, 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 20α-hydroxymethylprednisolone and 20-β-hydroxymethylprednisolone.

Excretion.

The metabolites are mainly excreted in the urine as glucuronides, sulphates and unconjugated compounds. Following intravenous (IV) administration of 14C-labelled methylprednisolone, 75% of the total radioactivity was recovered in the urine in 96 hours, 9% in faeces after 5 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

Solu-Medrol 40 mg Act-O-Vial system.

Monobasic sodium phosphate, dibasic sodium phosphate, lactose monohydrate, sodium hydroxide.

Diluent.

Water for injections.

Solu-Medrol 125 mg Act-O-Vial system.

Monobasic sodium phosphate, dibasic sodium phosphate, sodium hydroxide.

Diluent.

Water for injections.

Solu-Medrol 500 mg, 1 g and 2 g vials with diluent.

Monobasic sodium phosphate monohydrate, dibasic sodium phosphate, sodium hydroxide.

Diluent supplied with Solu-Medrol 500 mg, 1 g, and 2 g vials with diluent.

Benzyl alcohol, water for injections.

Solu-Medrol 500 mg and 1 g plain vials.

Monobasic sodium phosphate, dibasic sodium phosphate heptahydrate, sodium hydroxide.

6.2 Incompatibilities

To avoid compatibility and stability problems, whenever possible it is recommended that Solu-Medrol (methylprednisolone sodium succinate) be administered separately from other drugs and as either IV injection, through an IV medication chamber, microburette, or as an IV "piggy-back" solution. The IV 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 besylate, 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 unreconstituted product below 25°C.
When reconstituted using either the diluent provided, or 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

Solu-Medrol Powder for Injection is available in the following packages:
1 x 40 mg Act-O-Vial and diluent 1 mL in separate chambers.
1 x 125 mg Act-O-Vial and diluent 2 mL in separate chambers.
1 x 500 mg vial and 1 x diluent 8 mL.
1 x 1 g vial and 1 x diluent 15.6 mL.
1 x 2 g vial and 1 x diluent 31.2 mL.
1 x 500 mg plain vials.
5 x 500 mg plain vials.
1 x 1 g plain vials.
5 x 1 g plain vials.
Not all presentations and pack sizes are marketed.

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

Methylprednisolone sodium succinate USP, occurs as 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.

Chemical structure.


Molecular formula: C26H33NaO8.
Molecular weight: 496.53.

CAS number.

2375-03-3.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

Summary Table of Changes