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DILACORT 5 MG GASTRO-RESISTANT TABLETS

Active substance(s): PREDNISOLONE

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Summary of Product Characteristics
1

Name of the medicinal product
Dilacort 5 mg Gastro-Resistant Tablets
Prednisolone 5 mg Gastro-Resistant Tablets

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 5 mg prednisolone.
Excipients: Each tablet also contains 67.00 mg of lactose monohydrate, 0.98 mg of
ponceau 4R red (E124) and 0.0023 mg of sunset yellow FCF (E110).
For a full list of excipients, see section 6.1.

3

PHARMACEUTICAL FORM
Gastro-Resistant Tablet
Red, circular, deep biconvex, enteric coated tablets.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
Allergy and anaphylaxis: bronchial asthma, drug hypersensitivity reactions, serum
sickness, angioneurotic oedema, anaphylaxis.
Arteritis/collagenosis: giant cell arteritis/polymyalgia rheumatica, mixed connective
tissue disease, polyarteritis nodosa, polymyositis.
Blood disorders: haemolytic anaemia (auto-immune), leukaemia (acute and chronic
lymphocytic), lymphoma, multiple myeloma, idiopathic thrombo-cytopenic purpura.

Cardiovascular disorders: post-myocardial infarction syndrome, rheumatic fever
with severe carditis.
Endocrine disorders: primary and secondary adrenal insufficiency, congenital
adrenal hyperplasia.
Gastro-intestinal disorders: Crohn’s disease, ulcerative colitis, persistent coeliac
syndrome (coeliac disease unresponsive to gluten withdrawal), auto-immune chronic
active hepatitis, multisystem disease affecting liver, biliary peritonitis.
Hypercalcaemia: sarcoidosis, vitamin D excess.
Infections (with appropriate chemotherapy): helminthic infestations, Herxheimer
reaction, infectious mononucleosis, miliary tuberculosis, mumps orchitis (adult),
tuberculous meningitis, rickettsial disease.
Muscular disorders: polymyositis, dermatomyositis.
Neurological disorders: infantile spasms, Shy-Drager syndrome, sub-acute
demyelinating polyneuropathy.
Ocular disease: scleritis, posterior uveitis, retinal vasculitis, pseudo-tumours of the
orbit, giant cell arteritis, malignant ophthalmic Graves disease.
Renal disorders: lupus nephritis, acute interstitial nephritis, minimal change
glomerulonephritis.
Respiratory disease: allergic pneumonitis, asthma, occupational asthma, pulmonary
aspergillosis, pulmonary fibrosis, pulmonary alveolitis, aspiration of foreign body,
aspiration of stomach contents, pulmonary sarcoid, drug induced lung disease, adult
respiratory distress syndrome, spasmodic croup.
Rheumatic disorders: rheumatoid arthritis, polymyalgia rheumatica, juvenile chronic
arthritis, systemic lupus erythematosus, dermatomyositis, mixed connective tissue
disease.
Skin disorders: pemphigus vulgaris, bullous pemphigoid, systemic lupus
erythematosus, pyoderma gangrenosum.
Miscellaneous: sarcoidosis, hyperpyrexia, Behçets disease, immuno-suppression in
organ transplantation.

4.2

Posology and method of administration
The initial dosage may vary from 5mg to 60mg daily depending on the disorder being
treated. Divided daily dosage is usually used.
The following therapeutic guidelines should be kept in mind for all therapy with
corticosteroids:
Corticosteroids are palliative symptomatic treatment by virtue of their antiinflammatory effects; they are never curative.
The appropriate individual dose must be determined by trial and error and must be reevaluated regularly according to activity of the disease.
As corticosteroid therapy becomes prolonged and as the dose is increased, the
incidence of disabling side-effects increases.
In general, initial dosage shall be maintained or adjusted until the anticipated
response is observed. The dose should be gradually reduced until the lowest dose
which will maintain an adequate clinical response is reached. Use of the lowest
effective dose may also minimise side-effects (see 'Special warnings and special
precautions for use').
In patients who have received more than physiological dose for 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.
(See 'Special warnings and special precautions for use' and 'Undesirable effects')
During prolonged therapy, dosage may need to be temporarily increased during
periods of stress or during exacerbations of the disease (see 'Special warnings and
special precautions for use')

If there is lack of a satisfactory clinical response, the drug should be gradually
discontinued and the patient transferred to alternative therapy.
Intermittent dosage regimen: A single dose in the morning on alternate days or at
longer intervals is acceptable therapy for some patients. When this regimen is
practical, the degree of pituitary-adrenal suppression can be minimised.
Specific dosage guidelines: The following recommendations for some corticosteroidresponsive disorders are for guidance only. Acute or severe disease may require
initial high dose therapy with reduction to the lowest effective maintenance dose as
soon as possible. Dosage reductions should not exceed 5-7.5mg daily during chronic
treatment.
Allergic and skin disorders: Initial doses of 5-15mg daily are commonly adequate.
Collagenosis: Initial doses of 20-30mg daily are frequently effective. Those with
more severe symptoms may require higher doses.
Rheumatoid arthritis: The usual initial dose is 10-15mg daily. The lowest daily
maintenance dose compatible with tolerable symptomatic relief is recommended.
Blood disorders and lymphoma: An initial daily dose of 15-60mg is often necessary
with reduction after an adequate clinical or haematological response. Higher doses
may be necessary to induce remission in acute leukaemia.
Use in children: Although appropriate fractions of the actual dose may be used,
dosage will usually be determined by clinical response as in adults (see also 'Special
warnings and special precautions for use'). Alternate day dosage is preferable where
possible.
Use in 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 (see also 'Special warnings and special precautions for
use').

4.3

Contraindications
Systemic infections unless specific anti-infective therapy is employed.
Hypersensitivity to the active substance or any of the excipients listed in section 6.1.
Ocular herpes simplex because of possible perforation.

4.4

Special warnings and precautions for use
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), 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 of 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 and previous steroid psychosis.
Tumorigenicity: direct tumour-inducing effects of the glucocorticoids are not known,
but the particular risk that malignancies in patients undergoing immunosuppression
with these or other drugs will spread more rapidly is a well-recognised problem (see
section 4.5).
Calciphylaxis may occur very rarely during treatment with corticosteroids (see
section 4.8). Although calciphylaxis is most commonly observed in patients who have
end stage kidney failure, it has also been reported in patients taking corticosteroids
who have minimal or no renal impairment and normal calcium, phosphate and
parathyroid hormone levels. Patients/carers should be advised to seek medical advice
if symptoms develop.
Caution is necessary when oral corticosteroids, including prednisolone, are prescribed
in patients with the following conditions, and frequent patient monitoring is
necessary.


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



Inflammatory bowel disease: symptoms recurred in a patient with Crohn’s
disease on changing from conventional to enteric-coated tablets of prednisolone.
This was not an isolated occurrence in the author’s unit, and it was advocated that
only non-enteric coated prednisolone tablets should be used in Crohn’s disease,
and that the enteric coated form should be used with caution in any condition
characterised by diarrhoea or a rapid transit time.



Hypertension.



Congestive heart failure.



Liver failure.



Hepatic disease: In patients with acute and active hepatitis, protein binding of the
glucocorticoids will be reduced and peak concentrations of administered
glucocorticoids increased. Elimination of prednisolone will also be impaired.
There is an enhanced effect of corticosteroids in patients with cirrhosis.



Renal insufficiency.



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



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



Corticosteroid requirements may be reduced in menopausal and post-menopausal
women.



Patients with a history of severe affective disorders and particularly those with a
previous history of steroid-induced psychoses.



Also, existing emotional instability or psychotic tendencies may be aggravated by
corticosteroids including prednisolone.



Epilepsy, and/or seizure disorders



Peptic ulceration.



Previous steroid myopathy.



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.



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.

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
on alternate days. Frequent patient review is required to titrate the dose appropriately
against disease activity (see 'Posology and method of administration').
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.
In addition, 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. 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 mineralocorticoid 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.

Patients should carry “Steroid treatment” cards which give clear guidance on the
precautions to be taken to minimise risk and which provide details of prescriber, drug,
dosage and the duration of treatment.
Anti-inflammatory/Immunosuppressive effects and Infection: 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
infection such as septicaemia and tuberculosis may be masked and may reach an
advanced stage before being recognised when corticosteroids including prednisolone
are used. The immunosuppressive effects of glucocorticoids may result in activation
of latent infection or exacerbation of intercurrent infections.
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 should be advised to take particular care to avoid exposure to
measles, and to seek immediate medical advice if exposure occurs. Prophylaxis with
intramuscular normal immunoglobulin may be needed.
Administration of Live Vaccines: Live vaccines should not be given to individuals on
high doses of corticosteroids, due to impaired immune response. Live vaccines should
be postponed until at least 3 months after stopping corticosteroid therapy. (See also
section 4.5).
Ocular Effects: Prolonged use of corticosteroids may produce posterior subcapsular
cataracts and nuclear cataracts (particularly in children), exophthalmos, or increased
intraocular pressure, which may result in glaucoma with possible damage to the optic
nerves. Establishment of secondary fungal and viral infections of the eye may also be
enhanced in patients receiving glucocorticoids.
Corticosteroids should be used cautiously in patients with ocular herpes simplex
because of possible perforation.
Systemic glucocorticoid treatment can cause severe exacerbation of bullous exudative
retinal detachment and lasting visual loss in some patients with idiopathic central
serous chorioretinopathy (see Section 4.8).
Visual disturbance

Visual disturbance may be reported with systemic and topical corticosteroid use. If a
patient presents with symptoms such as blurred vison 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.
Cushing's disease: Because glucocorticoids can produce or aggravate Cushing's
syndrome, glucocorticoids should be avoided in patients with Cushing's disease
There is an enhanced effect of corticosteroids in patients with hypothyroidism.
Psychic derangements may appear when corticosteroids, including prednisolone, are
used, ranging from euphoria, insomnia, mood swings, personality changes, and severe
depression, to frank psychotic manifestations (see section 4.8).
Raised intracranial pressure: Raised intracranial pressure with papilloedema
(pseudotumour cerebri) associated with corticosteroid treatment has been reported in
both children and adults. The onset usually occurs after treatment withdrawal (see
section 4.8).
Paediatric population: Corticosteroids cause growth retardation in infancy,
childhood and adolescence, which may be irreversible, and therefore long-term
administration of pharmacological doses should be avoided. If prolonged therapy is
necessary, treatment should be limited to the minimum suppression of the
hypothalamo-pituitary adrenal axis and growth retardation. The growth and
development of infants and children should be closely monitored. Treatment should
be administered where possible as a single dose on alternate days.
There is an increased risk of nuclear cataracts (see Section 4.8).
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, the Lapp lactase
deficiency or glucose-galactose malabsorption should not take this medicine.
This medicine also contains sunset yellow FCF (E110) and ponceau 4R red (E124).
This may cause allergic reactions.

4.5

Interaction with other medicinal products and other forms of interaction
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 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.
Antacids: The absorption of prednisolone may be reduced by large doses of some
antacids such as magnesium trisilicate or aluminium hydroxide.
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.
CYP3A inhibitors: Co-treatment with CYP3A inhibitors, including cobicistatcontaining 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.
Non-steroidal anti-inflammatory drugs: Concomitant administration of ulcerogenic
drugs such as indometacin 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.
Prednisolone can lower plasma levels of isoniazid. Where a reduced response during
concurrent use is noted, dosage adjustment of isoniazid may be necessary.
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.
Antimuscarinics (Anticholinergics): Prednisolone has been shown to have
antimuscarinic activity. If used in combination with another antimuscarinic drug
could cause impairment to memory and attention in the elderly.
Antithyroids: Prednisolone clearance increased by the use of carbimazole and
thiamazole.
Cardiac Glycosides: Increased toxicity if hypokalaemia occurs with corticosteroids.
Ciclosporin: Concomitant administration of prednisolone and ciclosporin may result
in decreased plasma clearance of prednisolone (i.e. increased plasma concentration of
prednisolone). The need for appropriate dosage adjustment should be considered
when these drugs are administered concomitantly.
Cytotoxics: Increased risk of haematological toxicity with methotrexate.
Hormonal contraceptives: Oral contraceptives increased prednisolone concentrations
by 131%.
May increase AUC and reduce clearance in oral contraceptives containing
ethinylestradiol, mestranol, desogestrel, levonorgestrel, norgestrel or norethisterone.
Immunosuppressants: Tumorigenicity: direct tumour-inducing effects of the
glucocorticoids are not known, but the particular risk that malignancies in patients
undergoing immunosuppression with these or other drugs will spread more rapidly is
a well-recognised problem.
Liquorice: Glycyrrhizin can delay the clearance of prednisolone.
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.
Protease inhibitors: Ritonavir possibly increases plasma concentrations of
prednisolone and other corticosteroids by reduction in clearance of prednisolone
through the inhibition of P450 isoenzyme CYP3A4.
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.
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.

4.6

Fertility, pregnancy and lactation
Use in 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, in theory, occur in the neonate following
prenatal exposure to corticosteroids but usually resolves spontaneously following
birth and is rarely clinically important. Cataracts have been observed in infants born
to mothers treated with long-term prednisolone during pregnancy. As with all drugs,
cortico-steroids should only be prescribed when the benefits to the mother and child
outweigh the risks. When corticosteroids are essential however, patients with normal
pregnancies may be treated as though they were in the non-gravid state.
Patients with pre-eclampsia or fluid retention require close monitoring.
Use in breast-feeding: Corticosteroids are excreted in small amounts in breast milk.
Corticosteroids distributed into breast milk may suppress growth and interfere with
endogenous glucocorticoid production in nursing infants. Since adequate reproductive
studies have not been performed in humans with glucocorticoids, these drugs should
be administered to nursing mothers only if the benefits of therapy are judged to
outweigh the potential risks to the infant.
The concentration of the steroid in the milk can be between 5 and 25% of those in the
serum and the two roughly parallel one another after an oral dose.
There are no reports found regarding neonatal toxicity following exposure to
corticosteroids during lactation, however if maternal doses >40mg/day of
prednisolone is prescribed, the infant should be monitored for adrenal suppression.

4.7

Effects on ability to drive and use machines
The effect on the ability to drive or use machinery has not been evaluated. There is no
evidence to suggest that prednisolone may affect these abilities.

4.8

Undesirable effects
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 unknown.

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 are listed by MedDRA System Organ Classes.
Assessment of undesirable effects is based on the following frequency groupings:
Very common: ≥1/10
Common: ≥1/100 to <1/10
Uncommon: ≥1/1,000 to <1/100
Rare: ≥1/10,000 to <1/1,000
Very rare: <1/10,000
Not known: cannot be estimated from the available data

System Organ
Class

Frequency

Undesirable
Effect

Infections and
infestations

Not known

Increases
susceptibility to,
and severity of
infections1,
opportunistic
infections,
recurrence of
dormant
tuberculosis2,
oesophageal
candidiasis.

Blood and
lymphatic system
disorders

Not known

Leucocytosis.

Immune system
disorders

Not known

Hypersensitivity
including
anaphylaxis.

Endocrine
disorders

Not known

Suppression of the
hypothalamopituitary adrenal
axis3, cushingoid
facies, impaired

carbohydrate
tolerance with
increased
requirement for
antidiabetic
therapy,
manifestation of
latent diabetes
mellitus.
Metabolism and
nutrition disorders

Psychiatric
disorders

Not known

Sodium and water
retention,
hypokalaemic
alkalosis,
potassium loss,
negative nitrogen
and calcium
balance, glucose
intolerance and
protein catabolism.
Increase both high
and low density
lipoprotein
cholesterol
concentration in
the blood.
Increased appetite4.
Weight gain,
obesity,
hyperglycaemia,
dyslipidaemia.

Very rare

Calciphylaxis5.

Common

Irritability,
depressed and
labile mood,
suicidal thoughts,
psychotic
reactions, mania,
delusions,
hallucinations, and
aggravation of
schizophrenia,
behavioural
disturbances,
irritability, anxiety,
sleep disturbances,
and cognitive
dysfunction
including
confusion and
amnesia.

Not known

Euphoria,
psychological
dependence,

depression.
Nervous system
disorders

Not known

Depression,
insomnia,
dizziness,
headache, vertigo.
Raised intracranial
pressure with
papilloedema
(pseudotumor
cerebri)6.
Aggravation of
epilepsy, epidural
lipomatosis,
vertebrobasilar
stroke7.

Eye disorders

Not known

Glaucoma,
papilloedema,
posterior
subcapsular
cataracts, nuclear
cataracts
(particularly in
children),
exophthalmos,
corneal or scleral
thinning,
exacerbation of
ophthalmic viral or
fungal disease.
Vision, blurred (see
also Section 4.4).
Severe
exacerbation of
bullous exudative
retinal detachment;
lasting visual loss
in some patients
with idiopathic
central serous
chorioretinopathy8.

Ear and labyrinth
disorders

Not known

Vertigo.

Cardiac disorders

Not known

Congestive heart
failure in
susceptible
patients,
hypertension,
increased risk of
heart failure.

Increased risk of
cardiovascular
disease, including
myocardial
infarction9.
Vascular
disorders

Not known

Thromboembolism.

Gastrointestinal
disorders

Not known

Dyspepsia, nausea,
peptic ulceration
with perforation
and haemorrhage,
abdominal
distension,
abdominal pain,
diarrhoea,
oesophageal
ulceration, acute
pancreatitis.

Skin and
subcutaneous
tissue disorders

Not known

Hirsutism, skin
atrophy, bruising,
striae,
telangiectasia,
acne, increased
sweating, pruritis,
rash, urticaria.

Musculoskeletal
and connective
tissue disorders

Not known

Proximal
myopathy,
osteoporosis,
vertebral and long
bone fractures,
avascular
osteonecrosis,
tendon rupture,
tendinopathies
(particularly of the
Achilles and
patellar tendons),
myalgia, growth
suppression in
infancy, childhood
and adolescence.

Renal and urinary
disorders

Not known

Scleroderma renal
crisis*

Reproductive
system and breast
disorders

Not known

Menstrual
irregularity,
amenorrhoea.

General disorders
and
administration site
conditions

Not known

Fatigue, malaise,
impaired healing.

Investigations

Not known

Increased intraocular pressure,
may suppress
reactions to skin
tests.

1.

With suppression of clinical symptoms and signs.

2.

See Section 4.4 Special warnings and precautions for use.

3.

particularly in times of stress, as in trauma, surgery or illness.

4.

which may result in weight gain.

5.

see section 4.4 Special warnings and precautions for use.

6.

usually after treatment withdrawal.

7.

exacerbation of giant cell arteritis, with clinical signs of evolving stroke has been
attributed to prednisolone.

8.

See section 4.4 Special warnings and precautions for use.

9.

with high dose therapy.

*See section c)
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 section 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. Psychological
effects have been reported on withdrawal of corticosteroids.

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 at: www.mhra.gov.uk/yellowcard.

4.9

Overdose
Reports of acute toxicity and/or death following overdosage of glucocorticoids are
rare. No specific antidote is available; treatment is supportive and symptomatic.
Serum electrolytes should be monitored.

High systemic doses of corticosteroids caused by chronic use have been associated
with adverse effects such as neuropsychiatric disorders (psychosis, depression,
hallucinations), cardiac dysrhythmias and Cushing’s syndrome.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties
Pharmacotherapeutic group: glucocorticoid steroid, ATC code: H02A B06
Naturally occurring glucocorticoids (hydrocortisone and cortisone), which also have
salt-retaining properties, are used as replacement therapy in adreno-cortical
deficiency states. Their synthetic analogs are primarily used for their potent antiinflammatory effects in disorders of many organ systems.
Glucocorticoids cause profound and varied metabolic effects. In addition, they
modify the body’s immune responses to diverse stimuli.

5.2

Pharmacokinetic properties
Prednisolone is rapidly and apparently almost completely absorbed after oral
administration; it reaches peak plasma concentrations after 1-3 hours. There is
however wide inter-subject variation suggesting impaired absorption in some
individuals. Plasma half-life is about 3 hours in adults and somewhat less in children.
Its initial absorption, but not its overall bioavailability, is affected by food.
Prednisolone has a biological half-life lasting several hours, making it suitable for
alternate-day administration regimens.
Although peak plasma prednisolone levels are somewhat lower after administration of
Prednisolone Gastro-resistant Tablets and absorption is delayed, total absorption and
bioavailability are the same as after plain prednisolone. Prednisolone shows dose
dependent pharmacokinetics, with an increase in dose leading to an increase in
volume of distribution and plasma clearance. The degree of plasma protein binding
determines the distribution and clearance of free, pharmacologically active drug.
Reduced doses are necessary in patients with hypoalbuminaemia.
Prednisolone is metabolised primarily in the liver to a biologically inactive
compound. Liver disease prolongs the half-life of prednisolone and, if the patient has
hypoalbuminaemia, also increases the proportion of unbound drug and may thereby
increase adverse effects.
Prednisolone is excreted in the urine as free and conjugated metabolites, together with
small amounts of unchanged prednisolone.

Significant differences in the pharmacokinetics of prednisolone amongst menopausal
women have been described. The postmenopausal women had reduced unbound
clearance (30%), reduced total clearance and increased half-life of prednisolone.

5.3

Preclinical safety data
There are no pre-clinical data of relevance to the prescriber which are additional to
that already included in other sections of the SPC.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Lactose monohydrate
Microcrystalline cellulose
Pregelatinised maize starch
Magnesium stearate
Coating Components:Opadry white:
Hypromellose
Titanium dioxide (E171)
Triethyl citrate
Sorbic acid
Acryl-eze white:
Methacrylic acid – ethyl acrylate copolymer (1:1)
Talc
Titanium dioxide (E171)
Triethyl citrate
Colloidal anhydrous silica
Sodium bicarbonate
Sodium lauril sulfate
Opadry II Red:
Polyvinyl alcohol

Macrogol 3350
Ponceau 4R red (E124)
Talc
Titanium dioxide (E171)
Indigo carmine aluminium lake (E132)
Sunset yellow FCF (E110)

6.2

Incompatibilities
None known.

6.3

Shelf life
36 months.

6.4

Special precautions for storage
Store below 30 °C.

6.5

Nature and contents of container
PVC/PVdC/Aluminium blisters. Pack size of 28 tablets.

6.6

Special precautions for disposal
No special requirements.

7

MARKETING AUTHORISATION HOLDER
Crescent Pharma Limited
3&4 Quidhampton Business Units
Polhampton Lane
Overton

Hampshire
RG25 3ED
UK

8

MARKETING AUTHORISATION NUMBER(S)
PL 20416/0412

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
28/12/2012

10

DATE OF REVISION OF THE TEXT
14/12/2017

+ Expand Transcript

Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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