Consumer medicine information

Predmix Oral Liquid

Prednisolone

BRAND INFORMATION

Brand name

Predmix

Active ingredient

Prednisolone

Schedule

What is in this leaflet

This leaflet answers some common questions about PredMix Oral Liquid. It does not contain all the information that is known about PredMix Oral Liquid.

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 taking PredMix Oral Liquid against the benefits they expect it will have for you.

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

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

What PredMix Oral Liquid is used for

PredMix Oral Liquid contains prednisolone sodium phosphate which is changed to prednisolone after it enters the body.

Prednisolone belongs to a group of medicines called corticosteroids. It is a synthetic version of a naturally occurring body hormone called cortisol.

It works by entering inflammatory cells and blocking the inflammatory reaction. This medicine is only able to prevent or reduce symptoms of your condition, it does not cure it.

PredMix Oral Liquid is used in the treatment of many different conditions. Some of these conditions include: severe allergies, severe or chronic asthma, skin problems, arthritis, inflammatory diseases of the bowel, cancer and "auto-immune" diseases.

PredMix Oral Liquid is also used to prevent or reduce the symptoms of inflammation (such as swelling, redness, pain, tenderness or itching) in any part of the body. These symptoms can occur in response to injury or can be caused by many different conditions.

Ask your doctor if you have any questions about why PredMix Oral Liquid has been prescribed for you. Your doctor may have prescribed it for another reason.

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

There is no evidence that it is addictive.

Before you take it

When you must not take it

Do not take PredMix Oral Liquid if you have ever had an allergic reaction to:

prednisolone or prednisone
any of the ingredients listed at the end of this leaflet.

Symptoms of an allergic reaction may include shortness of breath, wheezing or difficulty in breathing; swelling of the face, lips, tongue or any other parts of the body; rash, itching or hives on the skin.

Do not take it if you have a current serious or uncontrolled infection, including fungal infections.

Do not take PredMix Oral Liquid after the expiry date printed on the label. It may have no effect at all or an entirely unexpected effect if you take it after the expiry date.

Do not take it if the packaging shows signs of having been tampered with.

Do not take this medicine to treat any other complaints unless your doctor has instructed you to do so.

Do not give this medicine to anyone else.

Before you start to take it

Tell your doctor if you are allergic to any other medicines or any foods, dyes or preservatives.

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

a current serious or uncontrolled infection, including fungal infections
recent surgery or serious injury
diabetes mellitus (sugar diabetes)
osteoporosis (softening of the bone)
a stomach ulcer or other stomach or intestinal problems
liver, kidney or heart disease
tuberculosis
epilepsy
muscle weakness
glaucoma (high pressure in the eye) or cataracts
thyroid disease
high blood pressure.

Do not take PredMix Oral Liquid if you are pregnant or plan to become pregnant. It is not generally recommended for use in pregnant women unless the benefits of treatment outweigh the risk to the unborn baby.

Do not take it if you are breast feeding or plan to breast feed. It is not recommended for use while breast feeding as this medicine is found in breast milk.

If you have not told your doctor about any of these things, tell them before you take PredMix Oral Liquid.

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 may interfere with PredMix Oral Liquid. These include:

antacids (in large amounts)
medicines for diabetes
some medicines for heart disease
medicines for removal of fluid (diuretics)
some medicines for epilepsy
some types of antibiotics
potassium or salt supplements
immunisations or vaccines
high dose aspirin
drugs which prevent blood clots.

These medicines may be affected by PredMix Oral Liquid or may affect how well it works. You may need to take different amounts of your medicine or you may need to take different medicines. Your doctor or pharmacist has a more complete list of medicines to be careful with or avoid while taking this medicine.

Use in children

PredMix Oral Liquid should only be used in children under your doctor's supervision.

If possible, children should not be exposed to common childhood illnesses such as chickenpox or measles while they are taking this medicine. They may suffer from more serious attacks of these illnesses if such exposure occurs.

Children should not be vaccinated with "live" vaccines against common childhood illnesses while they are taking it, as this may result in severe attacks of these illnesses.

Potentially serious side effects can occur in children and growing teenagers who are taking corticosteroids. Some of these include obesity, slowed growth, osteoporosis (softening of the bone) and changes in the adrenal glands.

Use in elderly

Elderly patients may be more sensitive to the effects or side effects of this medicine.

How to take it

How much to take

Follow all directions given to you by your doctor and pharmacist carefully. These directions may differ from the information contained in this leaflet.

The dose will depend on the condition being treated and your response to the treatment. Your initial dose will be maintained or adjusted until a satisfactory response is noted.

How to take it

Do not add anything to the PredMix Oral Liquid bottle itself.

Your dose of PredMix Oral Liquid can be mixed with milk, cordial, soft drink, soft food or you can take it by itself. You will soon know how you prefer to take the medicine.

When to take it

How often PredMix Oral Liquid can be taken may vary depending on what condition is being treated. It can be taken once daily, several times a day or on alternate days.

If you take it once a day or every second day, then it is best taken at breakfast time. If it needs to be taken more than once a day, then space it out during the day.

How long to take it

Continue taking PredMix Oral Liquid for as long as your doctor tells you. This will depend on your condition and on your response to treatment. Some people will need this medicine for only short periods of time whilst others may require long term therapy.

Do not miss any doses and do not stop taking the medicine even if you feel better. Missing doses may make your symptoms worse.

What to expect

Individuals will vary greatly in their response to PredMix Oral Liquid. Your doctor will check your progress at regular intervals.

If you forget to take it

If you miss a dose of this medicine the decision of whether you should take it or not will depend on how many times a day you take PredMix Oral Liquid.

If you are taking PredMix Oral Liquid:

once a day-
If you miss a dose and remember in less than 12 hours, take it straight away, then continue as normal the next day. Otherwise, skip that day's dose but be sure to take the next day's dose when it is due.
several times a day-
If you miss a dose and it is more than 2 hours before your next dose is due, take it straight away, then continue as you normally would. If it is less than 2 hours to your next dose, skip the dose you have missed but be sure to take the next dose when you are meant to.
on alternate days-
If you miss a dose and remember it the same morning, take it straight away then continue as you normally would. If you do not remember the missed dose until later, wait and take it the following morning. Then skip a day before continuing your regular dosage schedule.

Do not try to make up for missed doses by taking more than one dose at a time.

If you have trouble remembering when to take your medicine, ask your pharmacist for some hints.

If you take too much (Overdose)

Immediately telephone your doctor or Poisons Information Centre (telephone 13 11 26) for advice, or go to Accident and Emergency at the nearest hospital if you think that you or anyone else may have taken too much PredMix Oral Liquid. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

While you are taking it

Things you must do

Take PredMix Oral Liquid exactly as your doctor has prescribed. If you do not follow your doctor's instructions you may not get improvement in the symptoms of your condition. Try not to miss any doses and take the medicine even if you feel well.

Tell your doctor if your condition returns or becomes worse after your dose of PredMix Oral Liquid has been reduced or treatment has been stopped.

Tell your doctor immediately if you become pregnant while taking PredMix Oral Liquid.

Tell any other doctors, dentists and pharmacists who are treating you that you are taking PredMix Oral Liquid, especially if you are being started on any new medicines.

Tell your doctor, surgeon or dentist that you are taking PredMix Oral Liquid if you are about to undergo surgery or an operation. Your dose of this medicine may need to be increased to cover you during the stress of an operation.

Tell your doctor straight away if you are a diabetic, and you notice a change in the results of your blood or urine sugar tests. This medicine may affect your blood sugar levels as it can affect the body's ability to handle glucose. For diabetics, this means that your diabetes may become more severe. For others, diabetes may develop for the first time while taking corticosteroids such as PredMix Oral Liquid.

Ask your doctor when and how you should stop taking PredMix Oral Liquid.

If you have been taking it for a long time your doctor may gradually reduce the amount you are taking over a period of several days, weeks or months before stopping completely.

If you have been taking PredMix Oral Liquid for a short period of time, this may not apply.

Things you must not do

Do not give this medicine to anyone else even if their symptoms seem similar to yours.

Do not stop taking PredMix Oral Liquid suddenly unless advised by your doctor. If you stop taking it suddenly, the symptoms of your condition may return or you may develop symptoms of cortisol deficiency such as fainting, weakness, restlessness, nausea, vomiting, headache, dizziness, muscle weakness or joint pain.

Do not have any immunisations (particularly with "live" vaccines such as measles, oral polio or yellow fever) without your doctor's approval while you are being treated with PredMix Oral Liquid.

Things to be careful of

Avoid close contact with anyone who has a contagious disease such as measles or chickenpox. Exposure to such diseases while you are taking this medicine, particularly if large doses are being taken, can put you at greater risk of developing these diseases if you have not had them before.

Tell your doctor straight away if you think you have been exposed to chickenpox or measles.

Things to be aware of

As with any new medicine, you should take care when driving, operating machinery or drinking alcohol until you know how PredMix Oral Liquid affects you.

Check with your doctor or pharmacist before drinking alcohol while you are taking this medicine. If you drink alcohol while taking it you may find that stomach problems occur.

The signs and symptoms of infections such as fever or inflammation may be hidden by the anti-inflammatory action of PredMix Oral Liquid. You should see your doctor for medical advice for any but the most minor infections.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking PredMix Oral Liquid.

PredMix Oral Liquid helps most people who take it but it may have unwanted side effects in some people. 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 or pharmacist to answer any questions you may have.

Short term use

When PredMix Oral Liquid is taken for short periods of time it is unlikely to cause any problems.

Tell your doctor if you notice any of the following and they worry you:

mood changes
nausea (feeling sick)
vomiting
anorexia (which may result in weight loss)
increased appetite (which may result in weight gain)
stomach bloating or irritation
diarrhoea or constipation.

Long term use

When PredMix Oral Liquid is taken for long periods of time and in high doses the risk of side effects is greater.

Tell your doctor if you notice any of the following and they worry you:

general changes to the body:

bloating and rounding of the face (moon face)
headache
dizziness
weight gain
redistribution of body fat
water retention leading to swollen legs and feet, high blood pressure or an irregular heartbeat
cramps or weakness in the muscles of the arms and legs
slowed growth in children
irregular menstrual periods.

changes to the skin:

acne
red or flushed face
extra hair growth
red or purple streaks
easy bruising
skin thinning
increased sweating
poor wound healing.

changes to the immune system:

an increased seriousness or frequency of infections.

changes in behaviour:

excessive mood swings (such as changes in personality)
anxiety or nervousness
restlessness
trouble sleeping.

changes in eyes:

decreased or blurred vision
eyes sticking out too far
cataracts.

Tell your doctor immediately or go to casualty at your nearest hospital if you notice any of the following symptoms:

severe stomach or intestinal pain
epileptic fits
sudden changes to your vision
symptoms such as severe dizziness, fainting, weakness, chest pain or irregular heart beat
psychiatric disturbances.

These are all serious side effects of PredMix Oral Liquid which may occur with high doses and long term use. You may need urgent medical attention or hospitalisation.

Some side effects can only be detected by your doctor. So it is important to visit your doctor for regular check-ups when PredMix Oral Liquid is taken for long periods of time.

Such side effects may include:

osteoporosis or other changes in bone which can result in an increased chance of fractures due to brittleness or softening of the bone
changes in other hormone levels in your body
changes in the body's ability to handle glucose (steroid diabetes)
effects on the parathyroid and thyroid glands which control calcium and body metabolism
increased amounts of cholesterol in the blood
changes to your white blood cells
changes to your nervous system which may affect the way your nerves work
changed sperm count
increased blood pressure
slow heart rate
increased pressure in the skull.

Tell your doctor if you notice anything else that is making you feel unwell. Some people may get other side effects while using PredMix Oral Liquid.

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

After taking it

Storage

Keep PredMix Oral Liquid in the container it came in, tightly closed.

Store it in the refrigerator (between 2° and 8°C). Do not freeze.

Discard 4 weeks after opening.

Keep it where young children cannot reach it.

Disposal

If your doctor tells you to stop taking PredMix Oral Liquid, or you find that the expiry date has passed, ask your pharmacist what to do with any liquid you have left over.

Product description

What it looks like

PredMix Oral Liquid is a clear, colourless liquid. It is available in 30 mL bottles.

Ingredients

PredMix Oral Liquid contains 7.06 mg/mL prednisolone sodium phosphate (equivalent to 5 mg prednisolone) as the active ingredient.

It also contains the following inactive ingredients:

disodium edetate
methyl hydroxybenzoate
propylene glycol
propyl hydroxybenzoate
dibasic sodium phosphate dodecahydrate
monobasic sodium phosphate
water - purified.

Sponsor

Aspen Pharmacare Australia Pty Ltd
34-36 Chandos St
St Leonards NSW 2065
Australia

Australian Registration Number:
AUST R 67496.

This leaflet was revised in April 2021.

Published by MIMS June 2021

BRAND INFORMATION

Brand name

Predmix

Active ingredient

Prednisolone

Schedule

1 Name of Medicine

Prednisolone sodium phosphate.

2 Qualitative and Quantitative Composition

Predmix contains the active ingredient prednisolone sodium phosphate 7.06 mg/1 mL equivalent to prednisolone 5 mg/1 mL.
It contains excipients with known effect, methyl hydroxybenzoate and propyl hydroxybenzoate. For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Predmix is a clear, colourless liquid, free from haze and substantially free from particulate matter.

4 Clinical Particulars

4.1 Therapeutic Indications

Whenever corticosteroid therapy is indicated.

4.2 Dose and Method of Administration

Dosage should be individualised according to severity of condition and response of patient.

Children.

Asthma.

1 mg/kg once daily.

Croup.

1 mg/kg/dose every 8-12 hours for 48 hours.

Physiological replacement.

4-5 mg/m²/day (preferable to use shorter acting steroid to avoid growth suppression).

Infantile spasms, intractable epilepsy.

2 mg/kg/day.

Nephrotic syndrome.

2 mg/kg/day (max 80 mg/day) until protein free urine for 5 days. Increase to 4 mg/kg/day (max 120 mg/day) if no response within 28 days.

Autoimmune liver disease, Crohn's disease, ulcerative colitis.

2 mg/kg/day for initial control, reducing over 2 months to a maintenance dose of 5 mg/day or less (or cease).

Adults.

10-40 mg daily (up to 100 mg can be used in divided doses) reducing gradually when control is achieved to the lowest possible dose (5-20 mg).

4.3 Contraindications

Patients with active or doubtfully quiescent tuberculosis should not be given Predmix Oral Liquid except as an adjunct to treatment with tuberculostatic drugs.
Systemic fungal infections and known hypersensitivity to prednisolone or any of the excipients.

4.4 Special Warnings and Precautions for Use

Scleroderma renal crisis.

Caution is required in patients with systemic sclerosis because of an increased incidence of (possibly fatal) scleroderma renal crisis with hypertension and decreased urinary output observed with a daily dose of 15 mg or more prednisolone. Blood pressure and renal function (s-creatinine) should therefore be routinely checked. When renal crisis is suspected, blood pressure should be carefully controlled.
Corticosteroids should be used with caution in the presence of diminished cardiac reserve or congestive heart failure, in patients with diabetes mellitus, epilepsy, infectious diseases, chronic renal failure, uraemia, peptic ulcer, osteoporosis, psychoses or severe psychoneuroses and in elderly persons.
Corticosteroids may mask some signs of infection (such as fever and inflammation), and new infections may appear during their use. Infections with any pathogen, including viral, bacterial, fungal, protozoan, or helminthic infections, in any location in the body, may be associated with the use of corticosteroids alone or in combination with other immunosuppressant 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.
There may be decreased resistance to infection and inability to localise infection when corticosteroids are used. Children who are on immunosuppressant drugs are more susceptible to infection than healthy children. Chickenpox and measles, for example, can have a more serious course in these children. Particular care should be taken to avoid exposure in these children (and immunosuppressed adults).
Kaposi's sarcoma has been reported to occur in patients receiving corticosteroid therapy. Discontinuation of corticosteroids may result in clinical remission.

Withdrawal symptoms.

During prolonged treatment with corticosteroids, adrenal suppression and atrophy may occur and secretion of corticotrophin may be suppressed. Sudden withdrawal of Predmix Oral Liquid may then precipitate acute adrenal insufficiency with muscle weakness, hypotension, hypoglycaemia, headache, nausea, vomiting, restlessness and muscle and joint pain. Muscle weakness and stiff joints may persist for three to six months after treatment has been discontinued. In some instances, withdrawal symptoms may simulate a clinical relapse of the disease for which the patient has been under treatment.
Duration of treatment and dosage appear to be important factors in determining suppression of the pituitary-adrenal axis and response to stress on cessation of steroid treatment. Individual liability to suppression is also important. Some patients may recover normal function rapidly on discontinuing steroid therapy. In others, the production of hydrocortisone in response to the stress of infections, surgical operations or accident may be insufficient, and death results. Withdrawal of corticosteroids should therefore always be gradual unless sudden withdrawal is absolutely necessary.

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, 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.
Since complications of treatment with glucocorticoids are dependent on the size of the dose and 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.
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.
There is an enhanced effect of corticosteroids on patients with hypothyroidism and in those with cirrhosis.
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.
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.
Steroids 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; active or latent peptic ulcer; renal insufficiency; hypertension; osteoporosis and myasthenia gravis.
Growth and development of infants and children on prolonged corticosteroid therapy should be carefully observed.

Use in the elderly.

Corticosteroids should be used with caution in elderly persons.

Paediatric use.

Children on long term therapy should be monitored carefully for signs of serious adverse reactions including growth retardation, adrenal suppression, osteoporosis and obesity.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

The following drug interactions with corticosteroids have been selected on the basis of their potential clinical significance: antacids, antidiabetic agents (oral or insulin), digitalis glycosides, diuretics, drugs that induce hepatic microsomal enzymes, such as barbiturates, phenytoin and rifampicin; potassium supplements, ritodrine, sodium-containing medications or foods, somatrem or somatropin, vaccines, live viruses or other immunisations.
Drugs that induce hepatic microsomal enzymes, such as barbiturates, phenytoin and rifampicin may increase the clearance of corticosteroids and may require increases in corticosteroid dose to achieve the desired response.
Drugs such as troleandomycin and ketoconazole may inhibit the metabolism of corticosteroids and thus decrease their clearance. Therefore, the dose of corticosteroid should be titrated to avoid steroid toxicity. Corticosteroids may increase the clearance of chronic high dose aspirin. This could lead to decreased salicylate serum levels or increase the risk of salicylate toxicity when corticosteroid is withdrawn. Aspirin should be used cautiously in conjunction with corticosteroids in patients suffering from hypothrombinemia.
The effects of corticosteroids on oral anticoagulants are variable. There are reports of enhanced as well as diminished effects of anticoagulants when given concurrently with corticosteroids. Therefore, coagulation indices should be monitored to maintain the desired anticoagulant effect.
Convulsions have been reported with concurrent use of methylprednisolone and cyclosporin. Since concurrent use of these agents results in mutual inhibition of metabolism, it is possible that adverse effects associated with the individual use of either drug may be more apt to occur.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category A)
In animal experiments, corticosteroids have been found to cause malformations of various kinds (cleft palate, skeletal malformations) and abortion. These findings do not seem to be relevant to humans. Reduced placental and birth weight have been recorded in animals and humans after long-term treatment. Since the possibility of suppression of the adrenal cortex in the newborn baby after long term treatment must be considered, the needs of the mother must be carefully weighed against the risk to the fetus when prescribing these drugs. The short-term use of corticosteroids antepartum for the prevention of respiratory distress syndrome does not seem to pose a risk to the fetus or the newborn infant. Maternal pulmonary oedema has been reported with tocolysis and fluid overload.
The drug is excreted in breast milk, therefore, administration to nursing mothers is not recommended.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.8 Adverse Effects (Undesirable Effects)

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.
Short-term administration of Predmix Oral Liquid, even in doses at the high end of the dose range is unlikely to produce harmful effects associated with chronic usage, but short term administration may be associated with adverse effects related to the pharmacology of the drug.
The side effects associated with the use of corticosteroids in the large doses necessary to produce a therapeutic response result from excessive action on electrolyte balance, excessive action on other aspects of metabolism, including gluconeogenesis, the action on tissue repair and healing, and an inhibitory effect on the secretion of corticotrophin by the anterior pituitary gland. Disturbance of electrolyte balance is manifest in the retention of sodium and water, with oedema and hypertension and in the increased excretion of potassium with the development of hypokalaemic alkalosis. In extreme cases, cardiac failure may be induced.
Disturbances of electrolyte balance are common with the naturally occurring corticotrophin, cortisone, deoxycortone and hydrocortisone but are less frequent with the synthetic derivatives, prednisone and prednisolone. Other metabolic effects lead to mobilisation of calcium and phosphorus with osteoporosis and spontaneous fractures, nitrogen depletion and hyperglycaemia with accentuation or precipitation of the diabetic state. The insulin requirements of diabetic patients are increased and appetite is often increased.
The effect on tissue repair is manifest in peptic ulceration with haemorrhage and perforation, delayed wound healing and increased liability to infection. Increased susceptibility to all kinds of infection, including sepsis, fungus infections and viral infections have been reported.
Large doses of corticosteroids or of corticotrophins may produce symptoms typical of hyperactivity of the adrenal cortex, with moon face, buffalo hump, flushing, striae and acne, sometimes leading to a fully developed Cushing's syndrome. If administration of the hormone is discontinued immediately on the appearance of these symptoms, they are usually reversed but such sudden cessation may be dangerous. The dose of corticosteroid required to cause a decrease or absence of corticotrophin in the blood with consequent atrophy of the adrenal cortex and the time required for its occurrence are very variable. Acute adrenal insufficiency, with loss of consciousness, may occur during prolonged treatment or on cessation of treatment and may be precipitated by an infection or trauma.
Growth retardation in children has been reported, and in this respect, cortisone is only 1/10 as potent as prednisone and prednisolone. Other toxic effects include mental and neurological disturbances, intracranial hypertension and, on sudden reduction of dosage, during the treatment of rheumatoid arthritis, fatalities have been attributed to lesions of small arteries and arterioles similar to polyarteritis.
Infections may be masked since corticosteroids have marked anti-inflammatory and anti-pyretic properties and may produce a feeling of well being. The administration of corticosteroids may also cause a reduction in the number of circulating lymphocytes. Muscular weakness is an occasional side effect of most corticosteroids, particularly when they are taken in large doses.
Toxic effects occur with all corticosteroid preparations and their incidence rises steeply if dosage increases much above 8 mg daily of prednisolone or its equivalent.

Postmarketing reaction frequencies.

(> 5%).

Gastrointestinal.

Increased appetite; indigestion.

Neurological.

Nervousness or restlessness; insomnia.

(1-5%).

Dermatological.

Local allergic reaction.

Gastrointestinal.

Pancreatitis and ulcerative oesophagitis can occur. Peptic ulceration is an occasional complication, however, the high incidence of haemorrhage and perforation in these ulcers and the insidious nature of their development make them severe therapeutic problems. Some investigators believe that the available evidence does not support the conclusion that steroids cause ulcers. Others feel that only patients with rheumatoid arthritis have an increased risk of ulcers. It has been proposed that glucocorticoids alter the mucosal defence mechanism.

Ophthalmological.

Prolonged use of glucocorticoids may result in posterior subcapsular cataracts (particularly in children), exophthalmos, or increased intraocular pressure which may result in glaucoma or may occasionally damage the optic nerve and in rare cases, lead to blindness. Establishment of secondary fungal and viral infections of the eye may also be enhanced.

Biochemical.

All glucocorticoids increase gluconeogenesis. Glucose tolerance and sensitivity to insulin are decreased, but provided pancreatic islet function is normal, carbohydrate metabolism will not be noticeably deranged. Steroid diabetes has been reported to develop in one-fifth of patients treated with high glucocorticoid dosage. High dose corticosteroid therapy may induce marked hypertriglyceridaemia with milky plasma.

(< 1%).

Dermatological.

Dermatological adverse effects of corticosteroids include impaired wound healing, facial plethora, increased sweating, easy bruising, hirsutism, an acneform eruption on the face, chest and back, red striae on the thighs, buttocks and shoulders. Several months of high dose therapy can often result in thinning of the skin. Dermatological manifestations of hypersensitivity to corticosteroids include hives and/or allergic dermatitis, urticaria and angioedema. Corticosteroid induced purpura resembles senile purpura and usually occurs on extensor surfaces, the dorsum of the hand and the radial aspect of the forearm.

Neurological.

Adverse neurological effects have included headache, vertigo and increased motor activity, ischaemic neuropathy, EEG abnormalities and seizures. Large doses can cause behavioural and personality changes ranging from nervousness, euphoria or mood swings, to psychotic episodes which can include both manic and depressive states, paranoid states and acute toxic psychoses. It is no longer believed that previous psychiatric problems predispose to behavioural disturbances during therapy with glucocorticoids. Conversely, the absence of a history of psychiatric illness is no guarantee against the occurrence of psychosis during hormonal therapy.

Endocrine.

The endocrine effects of the glucocorticoids involve variously the hypothalamic-pituitary-adrenal axis, the parathyroid and the thyroid. There are also metabolic effects primarily involving the carbohydrates. Suppression of growth may occur in children. Cushing's syndrome may result from prolonged elevation of plasma glucocorticoid levels.
Corticosteroids have also been reported to increase or decrease the motility and number of sperm in some men. Disorders of menstruation are common.
Antagonism occurs between the parathyroids and hypercorticism. Latent hypoparathyroidism may be unmasked by administration of corticosteroids. The phosphate retention occurring in renal failure caused by adrenal insufficiency may also make hypoparathyroidism manifest.

Gastrointestinal.

Adverse gastrointestinal effects of corticosteroids include nausea, vomiting, anorexia (which may result in weight loss), diarrhoea or constipation, abdominal distension and gastric irritation.

Cardiovascular.

The mineralocorticoid activity of a steroid may lead to salt and water retention which can result in hypertension. Hypokalaemia can lead to arrhythmias and cardiac arrest.

Musculoskeletal.

Osteoporosis and vertebral compression fractures can occur in patients of all ages. Osteoporosis is an indication for withdrawal of therapy. Myopathy, characterised by weakness of the proximal musculature of arms and legs and their associated shoulder and pelvic muscles, is occasionally reported in patients taking large doses of corticosteroids. It may occur shortly after initiation of therapy and be sufficiently severe to prevent ambulation. It is an indication for withdrawal of therapy. Avascular aseptic necrosis of bone has often been described and preferentially involves the femoral and humeral head.

Withdrawal adverse effects.

Muscle weakness, hypotension, hypoglycaemia, headache, nausea, vomiting, restlessness and muscle and joint pain. Muscle weakness and stiff joints may persist for 3 to 6 months after discontinuation of therapy. Adverse reactions from corticosteroids are those resulting from withdrawal or from prolonged use of high doses.

The following adverse reactions have also been reported, however, there is no information on their incidence.

General.

Retardation of growth by long-term corticosteroid treatment in children.

Haematological.

Corticosteroids will increase the total WBC count, with an increase in neutrophils and a decrease in monocytes, lymphocytes and eosinophils.

Immunological.

The frequency and severity of clinical infections increase during glucocorticoid therapy.

Severe or life-threatening reactions.

Suppression of the hypothalamic-pituitary-adrenal axis is one of the consequences of repeated administration of glucocorticoids (see Section 4.4 Special Warnings and Precautions for Use). In some cases, acute adrenal insufficiency after a period of glucocorticoid treatment has proved fatal.

Neurological.

Latent epilepsy can be rendered manifest by corticosteroid treatment. Long-term treatment may result in benign intracranial hypertension.

Eye disorders.

Blurred vision.

Scleroderma renal crisis.

Frequency 'unknown'. Amongst the different subpopulations the occurrence of scleroderma renal crisis varies. The highest risk has been reported in patients with diffuse systemic sclerosis. The lowest risk has been reported in patients with limited systemic sclerosis (2%) and juvenile onset systemic sclerosis (1%).

Cardiac disorders.

Frequency 'unknown'. Bradycardia has been reported following high doses.

4.9 Overdose

There is no specific antidote. Toxic effects are signs of overdosage and should be treated symptomatically and dosage reduced or the drug withdrawn. During long courses of treatment, laboratory and metabolic studies should be made. Fluid retention should be watched for via fluid balance chart and daily weighing. Sodium intake may need to be reduced and potassium supplements may be necessary.
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.

Prednisolone sodium phosphate is readily hydrolysed in vivo to prednisolone and the pharmacology and clinical actions are therefore those of prednisolone.
Prednisolone is a synthetic adrenocortical steroid drug with predominantly glucocorticoid properties which include: promotion of gluconeogenesis, increased deposition of glycogen in the liver, inhibition of the utilisation of glucose, anti-insulin activity, increased catabolism of protein, increased lipolysis, stimulation of fat synthesis and storage, increased glomerular filtration rate and resulting increase in urinary excretion of urate (creatinine excretion remains unchanged) and increased calcium excretion. Some of the properties of prednisolone reproduce the physiological actions of endogenous glucocorticoids whereas others not reflecting any of the adrenal hormones' normal functions are seen with administration of larger doses of the drug.
Depressed production of eosinophils and lymphocytes occurs but erythropoiesis and production of polymorphonuclear leucocytes are stimulated. Anti-inflammatory processes (oedema, fibrin deposition, capillary dilatation, migration of leucocytes and phagocytosis) and the later stages of wound healing (capillary proliferation, deposition of collagen, cicatrisation) are inhibited.
Prednisolone can stimulate secretion of various components of gastric juice. Stimulation of the production of corticotrophin may lead to suppression of endogenous corticosteroids. Prednisolone has slight mineralocorticoid activity whereby entry of sodium into cells and loss of intracellular potassium is stimulated. This is particularly evident in the kidney where rapid ion exchange leads to sodium retention and hypertension.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Prednisolone is absorbed rapidly from the gastrointestinal tract. Maximum plasma concentrations (C_max) of approximately 140 nanogram/mL are achieved at 1.6 hours (t_max) following administration of a 10 mg dose (2 mL Predmix Oral Liquid). The elimination half life (t_1/2) of prednisolone is approximately 2 hours. Predmix Oral Liquid has been shown to be bioequivalent to prednisolone oral tablets (Panafcortelone).

Distribution.

Prednisolone is 90 to 95% bound to plasma proteins.

Metabolism.

Prednisolone is conjugated in the liver and to some extent in the kidney.

Excretion.

Prednisolone is excreted in the urine as free and conjugated metabolites, with 7-15% of an administered dose excreted as unchanged prednisolone.

5.3 Preclinical Safety Data

Genotoxicity.

In male rats, administration of prednisolone in the drinking water at a daily dose level of 0.4 mg/kg for two years caused an increased incidence of hepatocellular tumours. Similar results were obtained with triamcinolone acetonide and budesonide, indicating a class effect of glucocorticoids. The hepatocarcinogenic response to these drugs does not appear to be related to genotoxic activity.

Carcinogenicity.

The carcinogenic potential of prednisone has been evaluated in mice at oral doses up to 5 mg/kg/day for 18 months. No carcinogenic effect was noted in the mouse.

6 Pharmaceutical Particulars

6.1 List of Excipients

Propylene glycol, methyl hydroxybenzoate, propyl hydroxybenzoate, dibasic sodium phosphate dodecahydrate, monobasic sodium phosphate, disodium edetate and water-purified.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

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 at 2°-8°C. Refrigerate. Do not freeze.
Discard 4 weeks after opening.

6.5 Nature and Contents of Container

Bottles of 30 mL.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

It is a white or slightly yellow hygroscopic powder, soluble 1 in 3 or 4 of water and slightly soluble in alcohol. A 0.5% liquid has a pH of 7.5 to 9.0. Chemical name: 11β,17,21-trihydroxypregna-1,4-diene- 3,20-dione disodium 21-phosphate. Formula: C₂₁H₂₇Na₂O₈P, Molecular weight: 484.4.

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