Prednisolone Tablets BP 5 mg

Each tablet contains prednisolone 5 mg

Excipient(s) with known effect

Lactose

For the full list of excipients, see section 6.1.

Tablet

White, circular flat bevelled edged tablets with breakline.

In the management of corticosteroid sensitive dermatoses, rheumatic and collagen disorders, asthma including status asthmaticus, pulmonary fibrosis, adrenal hyperplasia, thrombocytopenic purpura and other haematopoietic dysplasias, gastrointestinal disorders, irido-choroditis.

Posology

A high initial dose is often given to achieve disease control, followed by a lower maintenance dose; however, in some cases short treatment courses are all that is required. The risk of side effects increases with dose and duration of corticosteroid therapy and so the dose of prednisolone should be the minimum required to achieve and maintain disease control. Individual doses should be determined and re-evaluated regularly according to disease activity. Doses should preferably be taken in the morning after breakfast to limit the steroid-induced suppression of cortisol secretion, alternate-day administration may be possible in some cases and has the benefit of further reducing pituitary-adrenal suppression.

Adults:

An initial dose of 10-20mg daily (up to 60mg in severe disease) is given to achieve disease control, this is followed by a gradual reduction to a maintenance dose of 2.5-15mg daily (higher doses may be required in some cases)

Children:

Prednisolone should be used only when indicated, at the lowest dose and for the shortest time possible to achieve the desired effect (see section 4.4)

Elderly:

Treatment of elderly patients, particularly if long-term, should take into consideration the more serious consequences of the common side effects of corticosteroids in old age (see section 4.4).

Treatment withdrawal; In patients who have received more than physiological doses of systemic corticosteroids (approximately 7.5mg prednisolone or equivalent) 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 be needed during withdrawal. If the disease is unlikely to relapse on withdrawal of systemic corticosteroids but there is uncertainty about hypothalamic-pituitary-adrenal (HPA) suppression, the dose of corticosteroid may be reduced rapidly to physiological doses. Once a daily dose equivalent to 7.5mg of prednisolone is reached, dose reduction should be slower to allow the HPA-axis to recover.

Abrupt withdrawal of systemic corticosteroid treatment, which has continued up to 3 weeks is appropriate if it is considered that the disease is unlikely to relapse. Abrupt withdrawal of doses of up to 40mg daily of prednisolone, or equivalent for 3 weeks is unlikely to lead to clinically relevant HPA-axis suppression, in the majority of patients. In the following patient groups, gradual withdrawal of systemic corticosteroid therapy should be considered even after courses lasting 3 weeks or less:

• Patients who have had repeated courses of systemic corticosteroids, particularly if taken for greater than 3 weeks.

• When a short course has been prescribed within one year of cessation of long-term therapy (months or years).

• Patients who may have reasons for adrenocortical insufficiency other than exogenous corticosteroid therapy.

• Patients receiving doses of systemic corticosteroid greater than 40mg daily of prednisolone (or equivalent).

• Patients repeatedly taking doses in the evening.

During prolonged therapy, dosage may need to be temporarily increased during periods of stress or during exacerbations of the disease

Method of administration

For oral use.

Hypersensitivity to the active substance(s) or to any of the excipients listed in section 6.1.

Systemic infection unless specific anti-infective therapy is employed.

Live vaccines should not be given to individuals with impaired immune responsiveness.

The antibody response to other vaccines may be diminished.

Patients with ocular herpes simplex due to the possibility of perforation.

A patient information leaflet should be supplied with this product.

Undesirable effects may be minimised by using the lowest effective dose for the minimum period, and by administering the daily requirement as a single morning dose or whenever possible as a single morning dose on alternate days. Frequent patient review is required to appropriately titrate the dose against disease activity (see section 4.2).

Patients should carry “steroid treatment” cards which give clear guidance on the precautions to be taken to minimise risk and which provide details of the prescriber, drug, dosage and the duration of treatment.

Patients and/or carers should be warned that potentially severe psychiatric adverse reactions may occur with systemic steroids (see section 4.8). Symptoms typically emerge within a few days or weeks of starting the treatment. Risks may be higher with high doses/systemic exposure (see also section 4.5 pharmacokinetic interactions that can increase the risk of side effects), although dose levels do not allow prediction of the onset, type, severity or duration of reactions. Most reactions recover after either dose reduction or withdrawal, although specific treatment may be necessary. Patients/carers should be encouraged to seek medical advice if worrying psychological symptoms develop, especially if depressed mood or suicidal ideation is suspected. Patients/carers should also be alert to possible psychiatric disturbances that may occur either during or immediately after dose tapering/withdrawal or systemic steroids, although such reactions have been reported infrequently.

Particular care is required when considering the use of systemic corticosteroids in patients with existing or previous history of severe affective disorders in themselves or in their first degree relatives. These would include depressive or manic-depressive illness, previous steroid psychosis, emotional instability or psychotic tendencies.

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.

Caution is necessary when corticosteroids, including prednisolone, are prescribed to patients with the following conditions and frequent patient monitoring is necessary:

• Diabetes mellitus or in those with a family history of diabetes.

• Glaucoma or in those with a family history of glaucoma.

• Hypertension or congestive heart failure.

• Liver failure. Corticosteroid effects may be enhanced in those with chronic liver disease and those with impairment of hepatic function.

• Epilepsy and/or seizure disorders.

• Osteoporosis: This is of special importance in post-menopausal females who are at particular risk.

• Patients with a history of severe affective disorders and particularly those with a previous history of corticosteroid induced psychoses.

• Peptic ulceration.

• Previous steroid myopathy.

• Renal insufficiency.

• Tuberculosis: Those with a history of, or X-ray changes characteristic of tuberculosis. The emergence of active tuberculosis can, however, be prevented by the prophylactic use of antituberculous therapy.

• Recent myocardial infarction (rupture).

• Chickenpox: Chickenpox is of particular concern since this normally minor illness may be fatal in immunosuppressed patients. Patients (or parents of children) without a definite history of chickenpox should be advised to avoid close personal contact with chickenpox or herpes zoster and if exposed they should seek urgent medical attention. Passive immunisation with varicella/zoster immunoglobulin (VZIG) is needed by exposed non-immune patients who are receiving systemic corticosteroids or who have used them within the previous 3 months; this should be given within 10 days of exposure to chickenpox. If a diagnosis of chickenpox is confirmed, the illness warrants specialist care and urgent treatment. Corticosteroids should not be stopped and the dose may need to be increased.

• Measles: Patients are advised to avoid exposure to measles, medical advice should be sought if exposure occurs. Prophylaxis with intramuscular normal immunoglobulin may be needed.

• Suppression of the inflammatory response and immune function increases the susceptibility to infections and their severity. The clinical presentation may often be atypical and serious infections such as septicaemia and tuberculosis may be masked and may reach an advanced stage before being recognized when corticosteroids including prednisolone are used. The immunosuppressive effects of glucocorticoids may result in activation of latent infection or exacerbation of intercurrent infections.

• The effect of corticosteroids may be enhanced in patients with hypothyroidism in those with chronic liver disease with impaired hepatic function.

• Live vaccines should not be given to individuals with impaired immune responsiveness. The antibody response to other vaccines may be diminished.

• Adrenal cortical atrophy develops during prolonged therapy and may persist for years after stopping treatment.

• Glucocorticoids should be used cautiously in patients with myasthenia gravis receiving anticholinesterase therapy.

• Because cortisone has been reported rarely to increase blood coagulability and to precipitate intravascular thrombosis, thromboembolism, and thrombophlebitis, corticosteroids should be used with caution in patients with thromboembolic disorders.

• Duchenne's muscular dystrophy: transient rhabdomyolysis and myoglobinuria may occur following strenuous physical activity. It is not known whether this is due to prednisolone itself or the increased physical activity.

• Corticosteroids may activate amoebiasis or strongyloidiasis and should be excluded before initiating treatment in those at risk or with suggestive symptoms.

• An anaesthetist should be aware that the patient is taking or has been taking a corticosteroid to avoid a precipitous fall in blood pressure during anaesthesia or in the following postoperative period.

Adrenocortical Insufficiency

Pharmacologic doses of corticosteroids administered for prolonged periods may result in hypothalamic-pituitary-adrenal (HPA) suppression (secondary adrenocortical insufficiency). The degree and duration of adrenocortical insufficiency produced is variable among patients and depends on the dose, frequency, time of administration, and duration of glucocorticoid therapy.

Acute adrenal insufficiency leading to a fatal outcome may occur if glucocorticoids are withdrawn abruptly. Drug-induced secondary adrenocortical insufficiency may therefore be minimized by gradual reduction of dosage (see below for advice on appropriate withdrawal of steroids). This type of relative insufficiency may persist for months after discontinuation of therapy; therefore, in any situation of stress occurring during that period, hormone therapy should be reinstituted. Since mineral corticoid secretion may be impaired, salt and/or a mineralocorticoid should be administered concurrently. During prolonged therapy any intercurrent illness, trauma, or surgical procedure will require a temporary increase in dosage; if corticosteroids have been stopped following prolonged therapy they may need to be temporarily re-introduced.

Administration of Live Vaccines

Live vaccines should be postponed until at least 3 months after stopping corticosteroid therapy. (See sections 4.3 and 4.5).

Cushing's disease

Because glucocorticoids can produce or aggravate Cushing's syndrome, glucocorticoids should be avoided in patients with Cushing's disease.

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.

Use in children

Corticosteroids cause growth retardation in infancy, childhood and adolescence, which may be irreversible and therefore long-term administration of pharmacological doses should be avoided. The growth and development of infants and children should be closely monitored during treatment. Treatment should be administered where possible as a single dose on alternate days.

Use in the elderly

Treatment of elderly patients, particularly if long term, should be planned bearing in mind the more serious consequences of the common side-effects of corticosteroids in old age, especially osteoporosis, diabetes, hypertension, hypokalaemia, susceptibility to infection and thinning of the skin. Close clinical supervision is required to avoid life-threatening reactions.

Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Withdrawal

In patients who have received more than physiological doses of systemic corticosteroids (approximately 7.5mg prednisolone or equivalent) 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 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 7.5mg of prednisolone is reached, dose reduction should be slower to allow the HPA-axis to recover.

Abrupt withdrawal of systemic corticosteroid treatment, which has continued up to 3 weeks is appropriate if it is considered that the disease is unlikely to relapse. Abrupt withdrawal of doses of up to 40mg daily of prednisolone, or equivalent for 3 weeks is unlikely to lead to clinically relevant HPA-axis suppression, in the majority of patients. In the following patient groups, gradual withdrawal of systemic corticosteroid therapy should be considered even after courses lasting 3 weeks or less:

• Patients who have had repeated courses of systemic corticosteroids, particularly if taken for greater than 3 weeks,

• When a short course has been prescribed within one year of cessation of long-term therapy (months or years),

• Patients who may have reasons for adrenocortical insufficiency other than exogenous corticosteroid therapy,

• Patients receiving doses of systemic corticosteroid greater than 40mg daily of prednisolone,

• Patients repeatedly taking doses in the evening.

During prolonged therapy any intercurrent illness, trauma or surgical procedure will require a temporary increase in dosage; if corticosteroids have been stopped following prolonged therapy they may need to be temporarily reintroduced.

Co-treatment with CYP3A inhibitors, including cobicistat-containing products, is expected to increase the risk of systemic side-effects. The combination should be avoided unless the benefit outweighs the increased risk of systemic corticosteroid side-effects, in which case patients should be monitored for systemic corticosteroid side-effects.

Hepatic microsomal enzyme inducers

Drugs that induce hepatic enzyme cytochrome P-450 (CYP) isoenzyme 3A4 such as phenobarbital, phenytoin, rifampicin, rifabutin, carbamazepine, primidone and aminoglutethimide may reduce the therapeutic efficacy of corticosteroids by increasing the rate of metabolism. Lack of expected response may be observed and dosage of prednisolone tablets may need to be increased.

Hepatic microsomal enzyme inhibitors

Drugs that inhibit hepatic enzyme cytochrome P-450 (CYP) isoenzyme 3A4 (e.g. ketoconazole, troleandomycin) may decrease glucocorticoid clearance. Dosages of glucocorticoids given in combination with such drugs may need to be decreased to avoid potential adverse effects.

Antidiabetic agents:

Glucocorticoids may increase blood glucose levels. Patients with diabetes mellitus receiving concurrent insulin and/or oral hypoglycemic agents may require dosage adjustments of such therapy.

Non-steroidal anti-inflammatory drugs:

Concomitant administration of ulcerogenic drugs such as indomethacin during corticosteroid therapy may increase the risk of GI ulceration. Aspirin should be used cautiously in conjunction with glucocorticoids in patients with hypoprothrombinaemia. Although concomitant therapy with salicylate and corticosteroids does not appear to increase the incidence or severity of GI ulceration, the possibility of this effect should be considered. Serum salicylate concentrations may decrease when corticosteroids are administered concomitantly. The renal clearance of salicylates is increased by corticosteroids and steroid withdrawal may result in salicylate intoxication. Salicylates and corticosteroids should be used concurrently with caution. Patients receiving both drugs should be observed closely for adverse effects of either drug.

Antibacterials

Rifamycins accelerate metabolism of corticosteroids and thus may reduce their effect. Erythromycin inhibits metabolism of methylprednisolone and possibly other corticosteroids.

Anticoagulants:

Response to anticoagulants may be reduced or less often, enhanced by corticosteroids. Close monitoring of the INR or prothrombin time is required to avoid spontaneous bleeding.

Antiepileptics:

Carbamazepine, phenobarbital, phenytoin and primidone accelerate metabolism of corticosteroids and may reduce their effect.

Antifungals:

Risk of hypokalaemia may be increased with amphotericin, therefore concomitant use with corticosteroids should be avoided unless corticosteroids are required to control reactions; ketoconazole inhibits metabolism of methylprednisolone and possibly other corticosteroids.

Antivirals:

Ritonavir possibly increases plasma concentrations of prednisolone and other corticosteroids.

Cardiac Glycosides

Increased toxicity if hypokalaemia occurs with corticosteroids.

Cytotoxics:

Increased risk of haematological toxicity with methotrexate.

Mifepristone:

Effect of corticosteroids may be reduced for 3-4 days after mifepristone.

Vaccines:

Live vaccines should not be given to individuals with impaired immune responsiveness. The antibody response to other vaccines may be diminished.

Oestrogens:

Oestrogens may potentiate the effects of glucocorticoids and dosage adjustments may be required if oestrogens are added to or withdrawn from a stable dosage regimen.

Somatropin:

Growth promoting effect may be inhibited.

Sympathomimetics:

Increased risk of hypokalaemia if high doses of corticosteroids given with high doses of bambuterol, fenoteral, formoteral, ritodrine, salbutamol, salmeterol and terbutaline.

Antacids

can reduce the absorbtion of prednisolone if given in high doses. Indigestion remedies should not be taken at the same time of day as Prednisolone.

Corticosteroids

should not be used concurrently with retinoids and tetracyclines due to increased intracranial pressure.

Other:

The desired effects of hypoglycaemic agents (including insulin), antihypertensives and diuretics are antagonised by corticosteroids; and the hypokalaemic effect of acetazolamide, loop diuretics, thiazide diuretics, carbenoxolone and theophylline are enhanced.

Pregnancy

The ability of corticosteroids to cross the placenta varies between individual drugs, however, 88% of prednisolone is inactivated as it crosses the placenta. Administration of corticosteroids to pregnant animals can cause abnormalities of foetal development including cleft palate, intra-uterine growth retardation and effects on brain growth and development. There is no evidence that corticosteroids result in an increased incidence of congenital abnormalities, such as cleft palate/lip in man. However, when administered for prolonged periods or repeatedly during pregnancy, corticosteroids may increase the risk of intra-uterine growth retardation. Hypoadrenalism may occur in the neonate following prenatal exposure to corticosteroids but usually resolves spontaneously following birth and is rarely clinically important. Cataracts have also been rarely reported. As with all drugs, corticosteroids should be prescribed only when the benefits to mother and child outweigh the risks. When corticosteroids are essential, however, patients with abnormal pregnancies may be treated as though they were in the non-gravid state. Patients with pre‐eclampsia or fluid retention require close monitoring.

Lactation

Corticosteroids are excreted in small amounts in breast milk. However, doses of up to 40mg daily of prednisolone are unlikely to cause systemic effects in the infant. Infants of mothers taking higher doses than this may have a degree of adrenal suppression but the benefits of breast feeding are likely to outweigh any theoretical risk. Monitoring of the infant for adrenal suppression is advised.

If insufficient sleep occurs, the likelihood of impaired alertness may be increased; patients should make sure they are not affected before driving or operating machinery.

A wide range of psychiatric reactions including affective disorders (such as irritable, euphoric, depressed and labile mood, and suicidal thoughts), psychotic reactions (including mania, delusions, hallucinations, and aggravation of schizophrenia), behavioural disturbances, irritability, anxiety, sleep disturbances, and cognitive dysfunction including confusion and amnesia have been reported. Reactions are common and may occur in both adults and children. In adults, the frequency of severe reactions has been estimated to be 5-6%. Psychological effects have been reported on withdrawal of corticosteroids; the frequency is Not known.

The incidence of predictable undesirable effects, including hypothalamic-pituitary-adrenal suppression correlates with the relative potency of the drug, dosage, timing of administration and the duration of treatment ( see section 4.4). Undesirable effects may be minimised by using the lowest effective dose for the minimum period, and by administering the daily requirement as a single morning dose or whenever possible as a single morning dose on alternative days. Frequent patient review is required to appropriately titrate the dose against disease activity.

*Following high doses

**

Scleroderma renal crisis

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%).

***Withdrawal symptoms: Too rapid a reduction of corticosteroid dosage following prolonged treatment can lead to acute adrenal insufficiency, hypotension and death (see section 4.4 and 4.2). A steroid “withdrawal syndrome” seemingly unrelated to adrenocortical insufficiency may also occur following abrupt discontinuance of glucocorticoids.

This syndrome includes symptoms such as: anorexia, nausea, vomiting, lethargy, headache, fever, joint pain, desquamation, myalgia, arthralgia, rhinitis, conjunctivitis, painful itchy skin nodules weight loss, and/or hypotension. These effects are thought to be due to the sudden change in glucocorticoid concentration rather than to low corticosteroid levels.

Additional side effects in children and adolescents

Suppression of the hypothalamo-pituitary adrenal axis particularly in times of stress, as in trauma, surgery or illness, growth suppression in infancy, childhood and adolescence. Raised intracranial pressure with papilloedema (pseudotumor cerebri) in children, usually after treatment withdrawal.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation 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 via the Yellow Card Scheme; website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

In the event of an overdosage no specific antidote is available. Treatment is supportive and symptomatic. Serum electrolytes should be monitored

Pharmacotherapeutic group: Corticosteroids for systematic use, plain

ATC CODE: H02A B06

Prednisolone is one of the highly potent glucocorticoid steroids having anti-inflammatory, hormonal and metabolic effects qualitatively similar to those of hydrocortisone. Glucocorticoids cause profound and varied metabolic effects. In addition, they modify the body's immune responses to diverse stimuli.

Absorption:

Prednisolone is readily and almost completely absorbed from the gastrointestinal tract after oral administration.

Distribution:

Peak plasma concentrations are obtained 1-2 hours after oral administration. Prednisolone is extensively bound to plasma proteins, although less so than hydrocortisone. Prednisolone crosses the placenta and small amounts are excreted in breast milk.

Metabolism:

Prednisolone is mainly metabolised in the liver and has a usual plasma half-life of 2-3 hours. It has a biological half-life lasting several hours which makes it suitable for the alternate-day administration regimens which have been found to reduce the risk of adrenocortical insufficiency, yet provide adequate corticosteroid coverage in some disorders.

Its initial absorption, but not its overall bioavailability, is affected by food, hepatic or renal impairment and certain drugs.

Excretion:

It is excreted in the urine as free and conjugated metabolites, together with an appreciable proportion of unchanged prednisolone.

None stated

Lactose

Maize starch

Sodium starch glycollate

Stearic acid

Magnesium stearate

Colloidal silicon dioxide

Starch paste 15%w/w

Not applicable

5 years

Store below 25°C in a dry place, protect from light

Polypropylene tubes with low density polyethylene caps in pack sizes of 100, 250, 500 and 1000 tablets

Al/PVC blisters strips enclosed in an outer carton, pack sizes 28 or 56 tablets

Not all pack sizes may be marketed

No special instructions

Strides Pharma UK Ltd

Unit 4 Metro Centre

Tolpits Lane

Watford

Hertfordshire

WD18 9SS

PL 13606/0037

28 January 1997

08/09/2022