4 Corners Pharmacy Cortisone, corticosteroids, prednisone,

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Prednisone Prednisone

APO-PREDNISONE

Prednisone 1mg, 2.5mg, 5mg, 10mg, 20mg and 50mg tablets BP

Presentations

APO-PREDNISONE 1mg tablets are round, white, biconvex, 5.5mm in diameter and identified P over 1 on one side. Each tablet contains 1mg prednisone and typically weighs 80mg.

APO-PREDNISONE 2.5mg tablets are round, white, biconvex, 6.0mm in diameter and identified P over 2.5 on one side. Each tablet contains 2.5mg prednisone and typically weighs 87mg.

APO-PREDNISONE 5mg tablets are round, white, flat-faced with bevelled edges, 6.5mm in diameter and identified P over 5 on one side. Each tablet contains 5mg prednisone and typically weighs 94mg.

APO-PREDNISONE 10mg tablets are round, white, flat-faced with bevelled edges, 8.0mm in diameter with a breakline on one side. Each tablet contains 10mg prednisone and typically weighs 188mg.

APO-PREDNISONE 20mg tablets are round, red, biconvex, 6.5mm in diameter and identified P over 20 with a breakline on one side. Each tablet contains 20mg prednisone and typically weighs 97mg.

APO-PREDNISONE 50mg tablets are round, red, biconvex, 9.0mm in diameter. Each tablet contains 50mg prednisone and typically weighs 243mg.

Uses

Actions

Prednisone is a biologically inert glucocorticosteroid which is rapidly converted in the liver to its active metabolite prednisolone. Glucocorticosteroids chief pharmacological effects are upon gluconeogenesis, glycogen deposition and protein and calcium metabolism. Glucocorticoids possess marked anti-inflammatory, anti-allergic and anti-rheumatic properties where they decrease the vascular and cellular component of the inflammatory response. Immunosuppressant properties are also exhibited especially with pharmacological doses.

Prednisone is a potent therapeutic agent influencing the biochemical behaviour of most tissues in the body. When prednisone is compared with the naturally occurring glucocorticoids, cortisone and cortisol (hydrocortisone), its anti-inflammatory effects are 5 times more potent whilst its mineralocorticoid properties are less pronounced. The onset of action of prednisone varies considerably depending on the dose and condition for which it is used. Its duration of action is approximately 18 to 36 hours.

Pharmacokinetics

Prednisone is readily absorbed from the gastro-intestinal tract and has a preconversion biological half-life of about 60 minutes before hydroxylation in the liver to its active metabolite prednisolone. Prednisolone has a plasma half-life of 2 to 3 hours and is extensively bound to plasma proteins. There are wide inter-individual differences in the rate of metabolism of prednisolone. Prednisolone is metabolised primarily in the liver to biologically inactive metabolites (primarily the gluconoride and sulphate). Prednisone is excreted in the urine as free and conjugated metabolites together with an appreciable amount of unchanged prednisolone. The conversion of prednisone is probably not diminished by liver disease.

Indications

Glucocorticoids are used to suppress the clinical manifestations of disease in a wide range of disorders such as: bronchial asthma, emphysema, pulmonary fibrosis, allergic skin reactions, blood disorders including auto-immune haemolytic anaemia and idiopathic thrombocytopenic purpura, selected collagen and rheumatic disorders (but rarely rheumatoid arthritis), connective tissue disorders such as arteritis and systemic lupus erythematosus, inflammatory bowel disease such as ulcerative colitis and Crohn's disease, some hepatic disorders such as chronic active hepatitis, nephritic syndrome and other renal disorders, selected inflammatory ocular diseases, acute exacerbations of eczema, exfoliate dermatitis and pemphigus, and some neurological disorders such as infantile seizures (epilepsy) and sub-acute demyelinating polyneuropathy.

Miscellaneous uses include raised intracranial pressure, sarcoidosis, the neonatal respiratory distress syndrome, the gastric acid aspiration syndrome, acute rheumatic fever with carditis and occasionally hypercalcaemia. Glucocorticoids may be used in conjunction with antineoplastic agents in regimens for the management of malignant disease such as leukaemia. They are also used to suppress the rejection phenomenon in tissue transplants.

Dosage and Administration

The smallest dose which is effective or produces adequate control should be used since inhibition of corticotrophin secretion is related to dose and the duration of glucocorticoid therapy. Alternate day early-morning dosage regimens produce less suppression of the HPA (Hypothalmic-pituitary-adrenal) axis but may not always provide adequate control - this regimen is not recommended for treatment of haematological disorders, malignancies, ulcerative colitis or severe conditions.

It may be necessary to increase dosage temporarily during maintenance therapy or during a steroid withdrawal programme for flare-ups of the underlying disease or for major stress such as infection or trauma. When pharmacological doses of glucocorticoids are to be reduced or withdrawn the dosage must be tapered gradually; this will be limited by the underlying disease process and the recovery of the HPA axis. Sudden cessation can be dangerous.

Take with food and a full glass of water.

Adults:

The initial dose of prednisone is 10mg - 100mg daily in divided doses, as a single daily dose at 8.00am or as a double dose on alternate days.

The maintenance dose is usually 5mg to 20mg daily. The dose should be individualised according to the severity of the disease and the patient's response rather than by age or body weight.

The usual adult prescribing limit is up to 250mg daily.

Short Term Therapy:

20mg to 40mg daily with dosage reductions of 2.5mg or 5mg every 2 to 4 days depending on response.

Children:

For infants and children the dosage should be governed by the severity and expected duration of the disease and reaction to medication rather than a strict adherence to the ratio indicated by age or bodyweight. For the treatment of adrenocortical insufficiency the USPDI recommends that doses be based on body surface area. Typically, for children over 18 months of age, initial dosage is 0.5mg/kg daily. This dosage can be doubled or trebled until definitive remission occurs. Maintenance dose is 0.125 - 0.25mg/kg daily.

Contraindications

Acute infections (if anti-infective agents are not administered simultaneously).

Live virus immunisation

Uncomplicated viral hepatitis

Pancreatitis (except pancreatitis caused by sarcoidosis)

Systemic fungal infections

Warnings and Precautions

Ideally corticosteroid therapy should not be instituted until a definite diagnosis has been made since the clinical signs and symptoms of disease can be masked or inhibited.

Abrupt withdrawal of prednisone after chronic use may precipitate acute adrenal insufficiency as a result of the suppression of corticotrophin at the anterior pituitary. Symptoms of adrenal insufficiency include malaise, muscle weakness, mental changes, muscle and joint pain, desquamation of the skin, dyspnoea, anorexia, nausea and vomiting, fever, hypoglycaemia, hypotension and dehydration.

The withdrawal symptoms may simulate a clinical relapse of the disease for which the patient is undergoing treatment. Withdrawal of prednisone should always be gradual, the rate depending on the individual patient's response, the dose and duration of therapy.

A degree of inhibition of hypothalmo-pituitary-adrenocortical function may persist for 6 to 12 months after prolonged high-dose treatment is withdrawn; steroid therapy may need be re-instituted during periods of stress.

Glucocorticoids should only be used with great caution in patients with diabetes mellitus, chronic renal failure, psychosis, osteoporosis, quiescent tuberculosis, glaucoma, hypertension, congestive heart failure, thromboembolic disorders and uraemia. Caution is necessary in patients with peptic ulcers since glucocorticoids have been implicated in causing peptic ulceration.

Corticosteroid-induced elevation of blood pressure, salt and water retention and increased potassium excretion are possible with high doses of prednisone. Like all corticosteroids, prednisone increases calcium excretion.

The administration of prednisone may mask some signs of infection or allow new infections to develop. Decreased resistance and inability to localise infection may be noted.

It has been observed that in cerebral malaria, the use of corticosteroids was associated with prolongation of coma and a higher incidence of pneumonia and gastrointestinal bleeding. Corticosteroids may activate latent amoebiasis, therefore it is recommended that latent or active amoebiasis be ruled out before initiation of corticosteroid treatment in any patient who has spent time in the tropics or has unexplained diarrhoea.

Prolonged corticosteroid use may produce posterior, subcapsular cataracts and/or glaucoma with possible damage to the optic nerves and may enhance the establishment of secondary ocular infections due to fungi or viruses. Corticosteroids should be used cautiously in patients with ocular herpes simplex because of possible corneal perforation.

The use of prednisone in active tuberculosis should be restricted to those cases of fulminating or disseminated tuberculosis. The prednisone must be used in conjunction with an appropriate antituberculosis regimen.

Metabolic clearance of adrenocorticoids is decreased in hypothyroid patients.

Geriatric patients and postmenopausal women may be more likely to develop glucocorticoid induced osteoporosis.

The use of corticosteroids may cause psychic derangements ranging from euphoria, insomnia, mood swings, personality changes and severe depression to frank psychotic manifestations.

Corticosteroids should be used with caution in non-specific ulcerative colitis if there is a probability of impending perforation, abscess or other pyogenic infection.

Steroids may increase or decrease motility and number of spermatozoa in some patients.

Patients who have received high or prolonged doses of prednisone should be given supplementary corticosteroids to overcome periods of stress caused by anaesthesia, surgery or trauma.

Prednisone can decrease plasma anticholinesterase activity which may affect the progress or treatment of myasthenia gravis.

Use in Pregnancy and Lactation

Category A

Prednisone crosses the placenta and although there have been reports of foetal abnormalities in animal studies these findings do not seem to be relevant to humans. Use in pregnancy requires that the possible benefit to the mother be weighed against the potential hazards to the foetus.

Corticosteroids appear in breast milk but physiologic doses of 5mg or less of Prednisone per day are not considered likely to affect the infant adversely. However, the use of higher doses could suppress growth, interfere with endogenous corticosteroid production or cause other unwanted effects and is therefore not recommended.

Use in Children

Prednisone should be used with caution for long term therapy in children. Children and adolescents should be closely monitored for growth retardation, osteoporosis, avascular necrosis of the femoral heads, glaucoma or cataracts during prolonged therapy.

Adverse Effects

Adverse effects are generally related to dose and duration of treatment. Their incidence increases steeply if dosage exceeds 7.5mg prednisone daily. Adverse effects include:

Osteoporosis and spontaneous fractures due to mobilisation of calcium and phosphorus
Increased susceptibility to infection, worsening of existing infection and activation of latent infection. In addition the normal inflammatory responses and symptoms are reduced or masked.
Latent diabetes mellitus may be unmasked or existing disease aggravated due to gluconeogenesis and increased insulin demands.
Myopathy with muscle weakness and wasting due to mobilisation of tissue proteins in gluconeogenesis.
Weight gain, increased appetite, bruising, striae in the skin, hirsutism, flushing, acne and redistribution of body fat creating the typical moon face and "buffalo hump".
Pancreatitis
Posterior subcapsular cataracts
Retardation of growth in children may be seen after long term use
HPA axis suppression following doses which exceed physiological amounts
Psychological disturbances which can range from insomnia and slight mood changes to suicide attempts; these are more likely to occur in patients with prior psychological disorders. Psychological dependence can also occur.

Interactions

The therapeutic efficacy of prednisone may be reduced by concurrent administration of enzyme inducing drugs such as phenobarbitone and other barbituates, phenylbutazone phenytoin and rifampicin.

Conversely, prednisone may reduce the effects of anticholinesterases in myasthenia gravis, pancuronium, salicylates and insulin or oral hypoglycaemic drugs. The action of anticoagulants may be reduced by corticosteroids.

Excessive potassium loss may be experienced if glucocorticoids and potassium-depleting diuretics (such as frusemide and thiazides) or carbonic anhydrase inhibitors (such as acetazolamide) are given together.

Sodium and water retention may occur and the value of restricting dietary sodium intake should be considered.

Concurrent use of antacids with prednisone may decrease absorption of these glucocorticoids - efficacy may be decreased sufficiently to require dosage adjustments in patients receiving small doses of prednisone.