PREDSOLONE

MIMS Revision Date: 01 June 2021

1 Name of Medicine

Prednisolone.

2 Qualitative and Quantitative Composition

Predsolone tablets contain 1 mg of the active prednisolone.
List of excipients with known effects: lactose monohydrate. For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Round, flat, white scored tablet debossed with 'PL/1' on one side and plain on the other.

4 Clinical Particulars

4.1 Therapeutic Indications

Wherever corticosteroid therapy is indicated such as: pemphigus vulgaris, allergic dermatitis, eczema, exfoliative dermatitis, dermatitis herpetiformis, dermatitis medicamentosa, erythema multiforme, disseminated lupus erythematosus, dermatomyositis, polyarteritis nodosa, severe bronchial asthma and status asthmaticus, emphysema, pulmonary fibrosis, adrenal hyperplasia (adrenogenital syndrome), idiopathic thrombocytopenic purpura, acquired haemolytic anaemia, acute leukaemia, nephrotic syndrome, iridochoroiditis, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, rheumatic fever, gout, periarthritis of the shoulder.

4.2 Dose and Method of Administration

The severity, prognosis, expected duration of the disease, and the patient's reaction to medication are primary factors in determining dosage.
Despite the 1 mg tablet being scored, it should not be broken.
Adults. The initial adult dosage may range from 20 to 40 mg daily, but can be 60 to 80 mg daily if necessary, depending on the disease being treated. Maintenance dosage: usually 5 to 20 mg daily. In long term therapy the ideal dosage should not be greater than 40 mg per day so as to minimise side-effects. It is usually administered in 2-4 divided doses, or as a single daily dose after breakfast or on alternate days.
Alternate-day therapy. Alternate day therapy is the dosage regimen of choice for long-term oral glucocorticoid treatment of most conditions. In alternate-day therapy, a single dose is administered every other morning. This regimen provides relief of symptoms while minimizing adrenal suppression, protein catabolism, and other adverse effects. However, some patients may require daily glucocorticoid therapy because symptoms of the underlying disease cannot be controlled by alternate-day therapy.
Elderly. As for adults - though the dose should be the minimum necessary to achieve the desired therapeutic effect.
Children. Initial dosage: 0.5 mg/kg daily in three or four divided doses after food as in adults. This dosage can be doubled or trebled if necessary. Maintenance dosage: 0.125 to 0.25 mg/kg daily.
For infants and children, the recommended dosage should be governed by the same considerations as adults rather than by strict adherence to the ratio indicated by age or bodyweight.
The following therapeutic guidelines should be kept in mind for all therapy with corticosteroids. Dosage should be decreased or discontinued gradually when the drug has been administered for more than a few days to avoid the risk of relative adrenal insufficiency (see Section 4.4 Special Warnings and Precautions for Use).
Continued supervision of the patient after cessation of corticosteroids is essential, since there may be a reappearance of severe manifestations of the disease for which the patient was treated.
In general, initial dosage should be maintained or adjusted until the anticipated response is observed. The dose should then be gradually reduced until the lowest dose which will maintain an adequate clinical response is reached.
Stress and intercurrent illness. In patients on long term corticosteroid therapy subjected to stress from trauma or infection, steroid dosage should generally be increased to cover the stressful period. For mild infections without fever, no increase is necessary. For more serious infections, the dose of prednisone/ prednisolone should be doubled (to a maximum of 20 mg daily, if the usual dosage was below this).
Adrenocortical insufficiency. Drug induced secondary adrenocortical insufficiency may result from too rapid withdrawal of corticosteroids and may be minimised by gradual reduction of dosage (see Section 4.4 Special Warnings and Precautions for Use). 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 may need to be reinstituted. If the patient is receiving steroids already, dosage may have to be increased.

4.3 Contraindications

Uncontrolled infections; known hypersensitivity to prednisone or prednisolone, or any of the excipients in the tablet.

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 prednisone or prednisolone. Blood pressure and renal function (s-creatinine) should therefore be routinely checked. When renal crisis is suspected, blood pressure should be carefully controlled.
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.
Because Predsolone manifests little sodium retaining activity, the usual early sign of hydrocortisone overdosage (i.e. increase in bodyweight due to fluid retention) is not a reliable index of prednisolone overdosage. Hence, recommended dose levels should not be exceeded, and all patients receiving Predsolone should be under close medical supervision. All precautions pertinent to the use of hydrocortisone apply to Predsolone.
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, fresh 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 or congestive heart failure (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 post menopausal 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.
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. Immunization 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 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.
Tuberculosis. Patients with active or doubtfully quiescent tuberculosis should not be given Predsolone except as adjuncts to treatment with tuberculostatic drugs, as reactivation of the disease may occur. Chemoprophylaxis is indicated during prolonged corticosteroid therapy.
Visual disturbance. Visual disturbance may be reported with systemic and topical corticosteroid use. 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 which may include cataract, glaucoma or rare diseases such as central serous chorioretinopathy (CSCR) which have been reported after use of systemic and topical corticosteroids.
Check the following before 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, 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 renal impairment. See Section 4.4, Scleroderma renal crisis.
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, somatrem or somatropin, vaccines, live viruses or other immunisations.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility. No data available.
Use in pregnancy. (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 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 the newborn infant. Maternal pulmonary oedema has been reported with tocolysis and fluid overload.
Use in lactation. 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 Predsolone, even in massive dosages, 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.
More common reactions. Gastrointestinal. Adverse gastrointestinal effects of corticosteroids include nausea, vomiting, anorexia (which may result in weight loss), increased appetite (which may result in weight gain), 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.
Neurological. Adverse neurological effects have included headache, vertigo, insomnia, restlessness 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.
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.
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.
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.
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.
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.
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.
Less common reactions. 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.
Neurological. Latent epilepsy can be rendered manifest by corticosteroid treatment. Long term treatment may result in benign intracranial hypertension.
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.
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.
Post marketing. 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

Treatment is symptomatic with the dosage being reduced or the drug withdrawn.
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 is a synthetic corticosteroid with glucocorticoid and anti-inflammatory effects. Prednisolone exceeds hydrocortisone in glucocorticoid and anti-inflammatory activity, being about three times more potent on a weight basis than the parent hormone, but is considerably less active than hydrocortisone in mineralocorticoid activity.
Predsolone, like hydrocortisone, is a potent therapeutic agent influencing the biochemical behaviour of most tissues of the body.
The mechanism of action of corticosteroids is thought to be by control of protein synthesis. Corticosteroids react with receptor proteins in the cytoplasm of sensitive cells in many tissues to form a steroid-receptor complex.
Corticosteroids are palliative symptomatic treatment by virtue of their anti-inflammatory effects; they are never curative.
Clinical trials. No data available.

5.2 Pharmacokinetic Properties

Prednisolone is readily absorbed from the gastrointestinal tract, but whereas prednisolone already exists in a metabolically active form, prednisone must be converted in the liver to its active metabolite, prednisolone.
Absorption. Peak plasma concentrations are obtained 1 or 2 hours after oral administration and prednisolone has a usual plasma half-life of 2 to 4 hours. Its initial absorption, but not its overall bioavailability, is affected by food. Predsolone has high oral bioavailability.
Distribution. Prednisolone is 90 to 95% bound to plasma proteins.
Metabolism. Predsolone is conjugated in the liver and to some extent in the kidney.
Excretion. Predsolone is excreted in the urine as free and conjugated metabolites, together with an appreciable proportion of unchanged prednisolone. Predsolone crosses the placenta and small amounts are excreted in breast milk.

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 glucocorticosteroids. 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

Prednisolone tablets contain lactose monohydrate, povidone, maize starch, magnesium stearate and crospovidone.

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

1 mg [AUST R 99791]: HDPE bottles of 90*, 100, 1000* and bulk* tablets.
(* Not currently distributed in Australia.)

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

Prednisolone occurs as a white to practically white, odourless, crystalline powder. It is very slightly soluble in water and sparingly soluble in alcohol.
Chemical name: 11β,17,21-Trihydroxypregna-1,4-diene-3,20-dione (C₂₁H₂₈O₅). Molecular weight: 360.4.
Chemical structure.

CAS number. 50-24-8.

7 Medicine Schedule (Poisons Standard)

S4.

Date of First Approval

23 February 2004

Date of Revision

19 April 2021

Summary Table of Changes