Consumer medicine information

Cortate

Cortisone acetate

BRAND INFORMATION

Brand name

Cortate

Active ingredient

Cortisone acetate

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Cortate.

What is in this leaflet

This leaflet answers some common questions about CORTATE. It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking CORTATE 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 CORTATE is used for

CORTATE contains cortisone acetate as the active ingredient. It belongs to a group of medicines called corticosteroids which is a synthetic version of a naturally occurring cortisol hormone secreted by the adrenal glands in your body.

CORTATE is used in the treatment of many different conditions, including severe allergic reactions (such as reactions to drugs), severe asthma, severe itchy skin rashes, chronic inflammatory diseases and 'auto-immune' diseases.

CORTATE is only able to prevent or reduce symptoms of your condition; it does not cure it.

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

CORTATE is not addictive.

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

Before you take it

When you must not take it

Do not take CORTATE if you have ever had an allergic reaction to:

  • any medicine containing cortisone
  • any of the tablet 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 an uncontrolled infection.

Do not take CORTATE after the expiry date (EXP) printed on the pack. If it has expired or is damaged, return it to your pharmacist for disposal.

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

If you are not sure whether you should start taking this medicine, talk to your doctor.

Before you start to take it

Tell your doctor if you have allergies to:

  • any other medicines
  • any other substances, such as foods, preservatives or dyes.

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

  • liver disease
  • stomach ulcer or other intestinal or stomach problems
  • kidney disease
  • high blood pressure
  • muscle weakness
  • epilepsy
  • diabetes mellitus (sugar diabetes)
  • osteoporosis (thinning or softening of the bone)
  • thyroid disease
  • glaucoma (high pressure in the eyes)
  • a current serious or uncontrolled infection
  • cataracts
  • alcoholism
  • heart problems
  • tuberculosis
  • emotional instability or psychotic tendencies.

It may not be safe for you to take CORTATE if you have any of these medical conditions.

Tell your doctor if you plan to have surgery. Your doctor may need to keep an eye on any changes to your condition caused by stress from the surgery. This may lead to adjustments to your dose.

Tell your doctor if you are pregnant or plan to become pregnant. Your doctor can discuss the possible risks and benefits of taking this medicine during pregnancy.

Tell your doctor if you are breast-feeding or plan to breastfeed. The active ingredient in CORTATE passes into breast milk and therefore there is a possibility that the breastfed baby may be affected. Your doctor can discuss with you the risks and benefits involved.

If you have not told your doctor about any of the above, tell them before you start taking CORTATE.

Taking other medicines

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

Some medicines and CORTATE may interfere with each other.

These include:

  • certain medicines used to treat heartburn and indigestion
  • medicines to treat diabetes mellitus (sugar diabetes)
  • certain medicines to treat heart failure
  • medicines used to help the kidneys get rid of salt and water by increasing the amount of urine produced (diuretics)
  • certain medicines used in epilepsy
  • medicines used to treat specific infections such as fungal infections or tuberculosis
  • potassium supplements
  • foods or medicines containing sodium
  • medicines to assist in growth
  • vaccines/immunisations
  • aspirin in certain patients
  • medicines used to prevent blood clots
  • specific medicines used to prolong labour
  • some medicines used for thyroid conditions
  • alcohol
  • the female hormone, estrogen.

CORTATE may influence the results of some laboratory tests.

It may suppress responses to skin tests.

These medicines may be affected by CORTATE or they may affect how well it works. You may need different amounts of your medicine, or you may need to take different medicines. Your doctor or pharmacist will advise you.

If you have not told your doctor or pharmacist about any of the above, tell them before you start taking CORTATE.

Use in children

Take special care when giving CORTATE to children.

It should only be given 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 CORTATE. They may suffer from more serious attacks of these illnesses if such exposure occurs.

Children should not be vaccinated with 'live' vaccines (e.g. oral polio, BCG tuberculosis, measles, mumps, rubella, yellow fever) against common childhood illness while they are taking CORTATE, 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 bones) and changes to the adrenal glands.

Use in the elderly

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

How to take it

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

If you do not understand the instructions on the bottle, ask your doctor or pharmacist for help.

How much to take

The dosage of CORTATE varies widely and depends on the patient, the condition being treated and the response to the treatment.

Your doctor or pharmacist will tell you how many tablets you will need to take each day and when to take them. This depends on your condition and whether or not you are taking any other medicines.

Any changes to your condition during therapy may also require your doctor to adjust your dose.

Tell your doctor if you believe that your condition is either getting better or worse.

You may require adjustments to your dose.

Tell your doctor if you feel that your current dose is not as effective as before.

Your doctor will review your situation and may recommend a dose adjustment.

How to take it

Swallow the tablets with a glass of water.

When to take it

How often you take CORTATE depends on what condition is being treated.

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

How long to take it

This will depend on your condition and your response to the treatment. Some people will need to take CORTATE for short periods of time whereas other people may require long term therapy.

Continue taking your medicine for as long as your doctor tells you. Don't stop taking it suddenly because your symptoms may worsen or come back.

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 your doctor has told you to take CORTATE.

  • If you take one dose a day- take the missed dose as soon as possible, then go back to your regular dosing schedule. If you do not remember until the next day, skip the missed dose and do not double the next one.
  • If you take several doses a daytake the missed dose as soon as possible, then go back to your regular dosing schedule.
  • If you take a dose 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 take a double dose to make up for the dose that you missed. This may increase the chance of you getting an unwanted side effect.

If you are not sure what to do, ask your doctor or pharmacist.

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

What to expect

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

If you take too much (overdose)

Immediately telephone your doctor or pharmacist or the Poisons Information Centre (telephone 13 11 26) for advice, or go to Accident and Emergency at your nearest hospital if you think that you or anyone else may have taken too much CORTATE. 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 CORTATE exactly as your doctor has prescribed.

If you do not follow the doctor's directions, 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 worsens after your dose of CORTATE has been decreased or treatment has been stopped.

Tell your doctor you are taking CORTATE before having any skin tests.

Tell your doctor if you get a serious infection or injury.

Tell any other doctors, dentists, and pharmacists who are treating you that you are taking CORTATE.

If you are about to be started on any new medicine, tell your doctor, dentist or pharmacist that you are taking CORTATE.

If you plan to have surgery that needs a general anaesthetic, tell your doctor or dentist that you are taking CORTATE. The trauma of the operation or surgery may mean that your dose of CORTATE needs to be adjusted to cover this stressful time.

Tell your doctor immediately if you are diabetic and if you notice any change in your blood or urine sugar readings. CORTATE 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 CORTATE.

If you become pregnant while taking CORTATE, tell your doctor or pharmacist.

Ask your doctor when and how you should stop taking CORTATE.

If you have been taking CORTATE for a long time, your doctor may gradually decrease the amount you are taking over a period of several days, weeks or months before stopping it completely. If you have been taking it for a short period of time, this may not apply.

Things you must not do

Do not give CORTATE to anyone else even if they have the same or a similar condition to you.

Do not take this medicine to treat any other complaints unless your doctor tells you to.

Do not stop taking it or lower the dosage without checking with your doctor or pharmacist. If you stop taking CORTATE suddenly, the symptoms of your condition may return or you may develop symptoms of certain hormone deficiencies such as fainting, weakness, restlessness, nausea, vomiting, headache, dizziness, muscle weakness or joint pain.

Do not have any immunisations (especially 'live' vaccines such as measles, oral polio or yellow fever) without your doctor's approval while you are taking CORTATE.

Things to be careful of

Avoid close contact with anyone who has a contagious disease such as chicken pox or measles.

Tell your doctor immediately if you think you have been exposed to chickenpox or measles. Exposure to such diseases while you are taking CORTATE, especially if large doses are prescribed, can put you at greater risk of developing these diseases if you have not had them before.

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 this medicine affects you.

Check with your doctor or pharmacist before drinking alcohol while you are taking CORTATE. If you drink alcohol while taking CORTATE, you may find that you develop stomach problems.

The signs and symptoms of infections such as fever or inflammation may be hidden by the anti-inflammatory action of CORTATE. You should see your doctor for medical advice for any but the most minor infections. Infections can bring on stress, which may affect your condition and require temporary dose adjustments.

Side effects

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

CORTATE helps most people, but it may have unwanted side effects in a few people. All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side effects.

If you are elderly you may have an increased chance of getting side effects.

Short term use
When CORTATE is taken for short periods of time, even at high doses, it is unlikely to produce harmful effects.

Long term use
When CORTATE 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 your body:

  • slowed growth in children
  • bloating or rounding of the face
  • cramps or weakness in the muscles of the arms and legs
  • water retention leading to swollen legs and feet
  • irregular heart beat
  • weight gain
  • headache
  • dizziness
  • irregular menstrual periods.

Changes to the immune system:

  • an increased seriousness or frequency of infections.

Changes to the gastrointestinal system:

  • nausea (feeling sick)
  • vomiting
  • indigestion, stomach pain or discomfort
  • increased appetite
  • diarrhoea or constipation
  • reduced appetite.

Changes in behaviour:

  • mood changes
  • anxiety or nervousness
  • restlessness
  • difficulty sleeping (insomnia)
  • personality changes.

Changes to the skin:

  • poor wound healing
  • red or flushed face
  • increased sweating
  • easy bruising
  • extra hair growth
  • acne
  • red or purple streaks on skin
  • skin thinning
  • itchy rash
  • unusual bleeding or bruising under the skin.

Changes in eyes:

  • cataracts
  • eyes sticking out too far
  • decreased or blurred vision.

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

  • severe stomach or intestinal pain
  • sudden changes in your vision
  • fits
  • major psychiatric changes
  • symptoms such as severe dizziness, fainting, weakness, chest pain or irregular heart beat (severe cortisol deficiency)
  • swelling of the face, lips, mouth, tongue or throat which may cause difficulty in swallowing or breathing.

These are serious side effects. You may need urgent medical attention or hospitalisation. Serious side effects are rare.

Some side effects can only be detected by your doctor. So it is importatnt to visit your doctor for regular check ups when CORTATE is taken for long periods of time.

Such side effects can include changes in:

  • strength of bones
  • blood sugar level (diabetes)
  • eye pressure (glaucoma)
  • cholesterol levels
  • hormone levels
  • sperm count
  • blood pressure (hypertension)
  • certain blood cells
  • the way nerves work
  • heart beat and rhythm.

Tell your doctor or pharmacist if you notice anything else that is making you feel unwell. Some people may get other side effects while taking CORTATE.

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

After taking it

Storage

Keep your tablets in the bottle until it is time to take them. If you take the tablets out of the bottle they will not keep well.

Keep your tablets in a cool dry place, protected from light, where the temperature stays below 30°C.

Do not store CORTATE or any other medicine in the bathroom or near a sink. Do not leave it on a windowsill or in the car on hot days. Heat and dampness can destroy some medicines.

Keep it where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

Dispose of the tablets where children cannot reach them.

If your doctor or pharmacist tells you to stop taking CORTATE or the tablets have passed their expiry date, ask your pharmacist what to do with any that are left over.

Product description

What it looks like

CORTATE tablets are available in two strengths; 5 mg or 25 mg.

The 5 mg tablet is a round, white, flat tablet. Available in bottles of 50 tablets.

The 25 mg tablet is a round, white, flat tablet with a break bar on one side. Available in bottles of 60 tablets.

Ingredients

Active ingredient:

CORTATE 5 mg - 5 mg cortisone acetate per tablet

CORTATE 25 mg – 25 mg cortisone acetate per tablet.

Inactive ingredients:

  • lactose monohydrate
  • povidone
  • magnesium stearate
  • maize starch
  • macrogol 6000 (5 mg tablet only).

CORTATE tablets do not contain gluten, sucrose, tartrazine or any other azo dyes.

Sponsor

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

Australian Registration Numbers:

5 mg tablet: AUST R 27912

25 mg tablet: AUST R 27910

This leaflet was revised in May 2017.

Published by MIMS August 2017

BRAND INFORMATION

Brand name

Cortate

Active ingredient

Cortisone acetate

Schedule

S4

 

1 Name of Medicine

Cortisone acetate.

2 Qualitative and Quantitative Composition

Cortate 5 mg are round, flat, white tablets containing 5 mg cortisone acetate as the active ingredient.
Cortate 25 mg are round, flat, white, scored tablets containing 25 mg cortisone acetate as the active ingredient.
Cortate tablets contain an excipient with known effect, lactose monohydrate. For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

See Section 2 Qualitative and Quantitative Composition.

4 Clinical Particulars

4.1 Therapeutic Indications

Addison's disease; allergic disorders including status asthmaticus; angioneurotic oedema, serum sickness and drug sensitisation; periarteritis nodosa; disseminated lupus erythematosus; giant cell arteritis.

4.2 Dose and Method of Administration

Dosage requirements are variable and must be individualised on the basis of the disease and the response of the patient. 25 mg once every 6 hours for an adult may be used to initiate treatment. Once remission is achieved, the daily dosage is reduced by 10 to 20 mg every few days until the optimum maintenance dose results. Acute and severe sensitivity or anaphylactic states may require much larger doses.

4.3 Contraindications

Hypersensitivity to cortisone acetate or any ingredients listed, see Section 6.1 List of Excipients, uncontrolled infections.

4.4 Special Warnings and Precautions for Use

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.
Patients, including those with Addison's disease, should be observed closely for signs that may require dosage adjustment, including changes in clinical status resulting from remissions or exacerbations of the disease, individual drug responsiveness, and the effect of stress (e.g. surgery, infection, trauma). During stress it may be necessary to increase dosage temporarily.
During prolonged corticosteroid therapy, adrenal suppression and atrophy may occur and secretion of corticotrophin may be suppressed. 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. The patient's liability to suppression is also variable. Some patients may recover normal function rapidly. In others, the production of hydrocortisone in response to the stress of infections, surgical operations or accident may be insufficient, and death results. Therefore, withdrawal of corticosteroids should always be gradual.
Abrupt withdrawal of corticosteroid therapy may precipitate acute adrenal insufficiency (see Section 4.8 Adverse Effects (Undesirable Effects)). In some cases, withdrawal symptoms may simulate a clinical relapse of the disease for which the patient has been under treatment.

Use with caution in the following circumstances.

Use with caution in nonspecific ulcerative colitis, if there is a probability of impending perforation, abscess or other pyogenic infection. Caution must also be used in diverticulitis, recent intestinal anastomoses, active or latent peptic ulcer, renal insufficiency, hypertension and myasthenia gravis, when steroids are used as direct or adjunctive therapy.
Use with caution in patients with epilepsy, diabetes mellitus, uraemia and in the presence of diminished cardiac reserve, congestive heart failure or thromboembolic disorders (see Section 4.8 Adverse Effects (Undesirable Effects)).
The possibility of development of osteoporosis should be an important consideration in initiating and managing corticosteroid therapy, especially in postmenopausal women (see Section 4.8 Adverse Effects (Undesirable Effects)).
The risk of gastrointestinal ulceration or hemorrhage is increased when alcohol is used concurrently with glucocorticoids.
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.
Use with caution in patients with emotional instability or psychotic tendencies.

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.

Infection.

Corticosteroids may mask some signs of infection (such as fever and inflammation), and new infections may appear during their use. There may be decreased resistance and inability to localise infection when corticosteroids are used. Susceptibility to infection is not specific for any particular bacterial or fungal pathogen.
Patients should not be vaccinated with live vaccines while on corticosteroid therapy. Other immunisation procedures should not be undertaken in patients on corticosteroid therapy, especially on high doses, because of possible hazards of neurological complications and lack of antibody response. Immunisation procedures may be undertaken in patients receiving corticosteroids as replacement therapy.
Children who are on immunosuppressant drugs are more susceptible to infections than healthy children. Chickenpox and measles, for example, can have a more serious or even fatal course in children on immunosuppressant doses of corticosteroids. In such children, or in adults who have not had these diseases, particular care should be taken to avoid exposure. If exposed, therapy with varicella zoster immune globulin (VZIG) or pooled intravenous immunoglobulin (IVIG), as appropriate, may be indicated. If chickenpox develops, treatment with antiviral agents may be considered.
Patients with active or doubtfully quiescent tuberculosis should not be given Cortate except as adjuncts to treatment with tuberculostatic drugs as reactivation of the disease may occur. Chemoprophylaxis is indicated during prolonged corticosteroid therapy.
Kaposi's sarcoma has been reported to occur in patients receiving corticosteroid therapy. Discontinuation of corticosteroids may result in clinical remission.

Check the following during use.

During long courses of treatment, laboratory and metabolic studies should be made. Fluid retention should be watched for via a fluid balance chart and daily weighing. Sodium intake may need to be reduced to less than 1 g daily and potassium supplements may be necessary.

Use in hepatic impairment.

Use with caution in patients with impaired hepatic function, as a reduction of dosage may be necessary. In treating chronic active liver disease with the drug, major adverse reactions such as vertebral collapse, diabetes, hypertension, cataracts and Cushing's syndrome occur in about 30% of patients.

Use in the elderly.

Caution is recommended for elderly patients as they are more susceptible to adverse reactions.

Paediatric use.

Children on long-term steroids must be carefully observed for potential serious adverse reactions such as obesity, growth retardation, osteoporosis and adrenal suppression.

Effects on laboratory tests.

Glucocorticoids may decrease I131 uptake and protein bound iodine concentrations, making it difficult to monitor the therapeutic response of patients receiving the drugs for thyroiditis. Glucocorticoids may produce false negative results in the nitroblue tetrazolium test for systemic bacterial infection. Glucocorticoids may suppress reactions to skin tests.

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 which induce hepatic microsomal enzymes, such as barbiturates, phenytoin and rifampicin; potassium supplements, ritodrine, sodium containing medications or foods, somatropin, vaccines, live viruses or other immunisations.
Convulsions have been reported with concurrent use of methylprednisolone and cyclosporin. Since concurrent use of these agents results in a mutual inhibition of metabolism, it is possible that adverse effects associated with the individual use of either drug may be more apt to occur.
Drugs that induce hepatic enzymes such as phenobarbital, phenytoin and rifampicin may increase the clearance of corticosteroids and may require increases in corticosteroid dose to achieve the desired response.
Drugs such as ketoconazole may inhibit the metabolism of corticosteroids and thus decreased their clearance. Therefore, the dose of corticosteroid should be titrated to avoid steroid toxicity.
Corticosteroids may increase the risk of salicylate toxicity when corticosteroid is withdrawn. Aspirin should be used cautiously in conjunction with corticosteroids in patients suffering from hypoprothrombinemia.
The effect of corticosteroids on oral anticoagulants is variable. There are reports of enhanced as well as diminished effects of anticoagulants when given concurrently with corticosteroids. Therefore, coagulation indices should be monitored to maintain the desired anticoagulant effect.
The various CYP450 isozymes responsible for these drug interactions are poorly understood due to the lack of information on the interaction between CYP450 isozymes and corticosteroids.

Antacids, cholestyramine, colestipol.

Decrease cortisone's effect by adsorbing the corticosteroid, decreasing the amount absorbed. Advise clinician to monitor patient carefully.

Cardiac glycosides.

Hypokalaemia may increase the risk of toxicity in patients also receiving cardiac glycosides. Avoid use together.

Diuretic or amphotericin B therapy.

Cortisone may enhance hypokalaemia associated with diuretic or amphotericin B therapy. Advise clinician to monitor serum blood levels closely, especially potassium.

Estrogens.

May reduce the metabolism of cortisone. The half-life of cortisone is then prolonged. Avoid use together.

Insulin, oral antidiabetics.

Cause hyperglycaemia. Dosage adjustment may be needed.

Isoniazid, salicylates.

When used together, cortisone increases the metabolism of isoniazid and salicylates. Use together cautiously.

Toxoids, inactivated vaccines.

Cortisone may have a diminished response to toxoids or inactivated vaccines. Avoid use together.

Alcohol.

Increased risk of gastric irritation and GI ulceration. Advise patient to avoid alcohol.

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 birthweight 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 corticosteroids. 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 newborn infant.
Corticosteroids may be associated with tocolysis (inhibition of uterine contraction) and maternal 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 http://www.tga.gov.au/reporting-problems.
Short-term administration of Cortate, even in large doses, is unlikely to produce harmful effects. The majority of adverse reactions from corticosteroids are those resulting from withdrawal or from prolonged use of high doses.
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 and water balance is manifest in sodium retention 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 corticotrophins, cortisone, deoxycortone and hydrocortisone but are less frequent with the synthetic derivatives, prednisone and prednisolone. Other metabolic effects include 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 can manifest as peptic ulceration with haemorrhage and perforation, delayed wound healing and increased liability to infection. Increased susceptibility to all infection, including sepsis, fungal and viral infection, has been reported.
Large doses of corticosteroids or corticotrophins may produce symptoms typical of hyperactivity of the adrenal cortex, with moonface, 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 one-tenth 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 attributed to lesions of small arteries and arterioles similar to polyarteritis.
Infections may be masked since corticosteroids have marked anti-inflammatory and antipyretic properties and may produce a feeling of well-being. The administration of corticosteroids may also cause a reduction in the number of circulating lymphocytes and eosinophils. 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 40 mg daily of cortisone 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. 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 the available evidence does not support the conclusion that steroids cause ulcers. Others feel that only patients with rheumatoid arthritis have an increased incidence of ulcers. It has been proposed that the 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 may not be significantly deranged. Steroid induced 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 acneiform 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 skin. Dermatologic manifestations of hypersensitivity to the corticosteroids include hives and/or allergic dermatitis, urticaria, and angioedema.
Corticosteroid induced purpura resembles senile purpura. This purpura usually occurs on extensor surfaces, dorsum of the hand, and radial aspect of the forearm.

Neurological.

Adverse neurological effects have included headache, vertigo and increased motor activity, ischemic 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.
Pseudotumor cerebri and paresthesia have also been reported.

Endocrine.

The endocrine effects of the glucocorticoids involve variously the hypothalamic pituitary adrenal axis, the parathyroid and 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 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.
Hypocalcaemia, hypercholesterolemia, decreased serum thyroxine and triiodothyronine levels have also been reported.

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 also result in hypertension. Hypokalaemia can lead to arrhythmias and cardiac arrest. Heart failure, thromboembolism and thrombophlebitis have also been reported.

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 soon after treatment is begun 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 three to six months after discontinuation of treatment. Adverse reactions from corticosteroids are those resulting from withdrawal or from prolonged use of high doses.
In patients who have received systemic corticosteroids for greater than 3 weeks, withdrawal should not be abrupt. How dose reduction should be carried out depends largely on whether the disease is likely to relapse as the dose of systemic corticosteroids is reduced. Clinical assessment of disease activity may therefore be needed during withdrawal. If the disease is unlikely to relapse on withdrawal of systemic corticosteroids but there is uncertainty about HPA suppression, the dose of systemic corticosteroid may be reduced rapidly to physiological doses. Once a daily dose equivalent to 7.5 mg of prednisolone is reached, dose reduction should be slower to allow the HPA axis to recover.
The following adverse reactions have also been reported, however there is no information on their incidences.

General.

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

Eye disorders.

Blurred vision.

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.

Serious 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.

4.9 Overdose

Acute ingestion, even in massive doses, is rarely a clinical problem. Toxic signs and symptoms rarely occur if the drug is used for less than 3 weeks, even at large dosage ranges. However, chronic use causes adverse physiologic effects.
For information on the management of overdose, contact the Poisons Information Centre for advice on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

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

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Distribution.

The biological half-life of hydrocortisone is about 100 minutes and it is more than 90% bound to plasma proteins.

Metabolism.

Cortisone is inactive until the 11-oxo group is reduced by 11-β-hydroxy-dehydrogenase to form the active product, hydrocortisone (or cortisol). The relative bioavailability of cortisone compared to hydrocortisone is approximately 80%, with the difference being attributed to a small amount of metabolism of cortisone to the inactive tetrahydrocortisone.

Excretion.

The main elimination route of hydrocortisone is by metabolism to tetrahydrocortisone. There is little conversion of hydrocortisone back to cortisone. Tetrahydrocortisone and tetrahydrocortisol are excreted in the urine, mainly conjugated as glucuronides, together with a very small proportion of unchanged hydrocortisone.
In patients with cirrhosis, the conversion of cortisone to hydrocortisone is preserved but the half-life of hydrocortisone is prolonged markedly to around 5 hours. In patients with thyrotoxicosis, there is a greater rate of conversion for cortisone to hydrocortisone and a shortened half-life of hydrocortisone to around 1 hour.

5.3 Preclinical Safety Data

Genotoxicity/ 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. 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 glucocorticosteroids. The hepatocarcinogenic response to these drugs does not appear to be related to genotoxic activity.

6 Pharmaceutical Particulars

6.1 List of Excipients

Cortate 5 mg tablets contain lactose monohydrate, macrogol 6000, povidone, magnesium stearate and maize starch.
Cortate 25 mg tablets contain lactose monohydrate, povidone, magnesium stearate and maize starch.

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 below 30°C.

6.5 Nature and Contents of Container

Cortate 5 mg.

Pack sizes of 50, 100 and bulk tablets in HDPE bottles.

Cortate 25 mg.

Pack sizes of 30, 60, 100, 1000 and bulk tablets in HDPE bottles.
(Note: not all pack sizes are available).

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

Cortisone acetate is a white or practically white, odourless, crystalline powder. It is stable in air and is insoluble in water.
Chemical name: 21-(acetyloxy)-17-hydroxypregn- 4-ene-3,11,20-trione. Empirical formula: C23H30O6, molecular weight: 402.49.

Chemical structure.


CAS number.

50-04-4.

7 Medicine Schedule (Poisons Standard)

S4.

Summary Table of Changes