Predsol Suppositories.

5mg prednisolone as the sodium phosphate ester.

For excipients, see 6.1

Suppository

Prednisolone is a glucocorticosteroid which is about four times as potent as hydrocortisone on a weight for weight basis.

Predsol Suppositories are indicated for the treatment of haemorrhagic and granular proctitis and the anal complications of Crohn's disease.

Rectal administration in adults and children:

One suppository inserted at night and one in the morning after defaecation. When the response is good, treatment is usually continued for some months. If symptoms recur later, treatment should be resumed.

Systemic or local infection unless specific anti-infective therapy is employed.

Hypersensitivity to any ingredient.

Although Predsol Suppositories are applied locally, it should be borne in mind that there is likely to be substantial systemic absorption, especially when the bowel is inflamed.

Undesirable effects may be minimised by using for a minimum period. Frequent patient review is required to monitor therapeutic effect against disease activity.

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 recognised.

Chickenpox is of particular concern since this normally minor illness may be fatal in immunosuppressed patients. Patients 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.

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.

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

Corticosteroid treatment may reduce the response of the pituitary adrenal axis to stress, and relative insufficiency can persist for up to a year after withdrawal of prolonged therapy. Withdrawal of corticosteroids after prolonged therapy must therefore always be gradual to avoid acute adrenal insufficiency, being tapered off over weeks or months according to the dose and duration of treatment. 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.

Use with caution in patients with myasthenia gravis, non-specific ulcerative colitis, diverticulitis and fresh intestinal anastamoses.

Special precautions:

Particular care is required when considering the use of systemic corticosteroids in patients with the following conditions and frequent patient monitoring is necessary.

A. Osteoporosis (post-menopausal females are particularly at risk).

B. Hypertension or congestive heart failure.

C. Existing or previous history of severe affective disorders (especially previous steroid psychosis).

D. Diabetes mellitus (or a family history of diabetes).

E. History of tuberculosis.

F. Glaucoma (or a family history of glaucoma).

G. Previous corticosteroid-induced myopathy.

H. Liver failure - blood levels of corticosteroid may be increased, (as with other drugs which are metabolised in the liver).

I. Renal insufficiency.

J. Epilepsy.

K. Peptic ulceration.

L. Hypothyroidism.

M. Recent myocardial infarction.

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.

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 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 of systemic steroids, although such reactions have been reported infrequently.

Use in the elderly:

The common adverse effects of systemic corticosteroids may be associated with more serious consequences in old age, especially osteoporosis, hypertension, hypokalaemia, diabetes, susceptibility to infection and thinning of the skin. Close clinical supervision is required to avoid life-threatening reactions.

Systemic absorption of prednisolone should be borne in mind, especially when there is local inflammation. Thus the following interactions are possible:

Analgesics:

Increased risk of gastro-intestinal bleeding and ulceration with aspirin and NSAIDs; the renal clearance of salicylates is increased by corticosteroids and steroid withdrawal may result in salicylate intoxication.

Antibacterials:

Rifamycins accelerate metabolism of corticosteroids (reduced effect); erythromycin inhibits metabolism of methylprednisolone and possibly other corticosteroids. Fluoroquinolones - Increased risk of tendon rupture.

Anticoagulants:

The efficacy of coumarin anticoagulants may be enhanced by concurrent corticosteroid therapy and close monitoring of the INR or prothrombin time is required to avoid spontaneous bleeding.

Antidiabetics:

Antagonism of hypoglycaemic effect.

Antiepileptics:

Carbamazepine, phenobarbital, phenytoin and primidone accelerate metabolism of corticosteroids (reduced effect).

Antifungals:

Increased risk of hypokalaemia with amphotericin (avoid concomitant use unless corticosteroids are required to control reactions); ketoconazole inhibits metabolism of methylprednisolone and possibly other corticosteroids.

Antihypertensives:

Antagonism of hypotensive effect.

Anticholinesterases:

Decreased effect of anticholinesterases in myasthenia gravis.

Antivirals:

Ritonavir possibly increases plasma concentration of prednisolone.

Cardiac Glycosides:

Increased toxicity if hypokalaemia occurs with corticosteroids.

Ciclosporin:

Increased plasma concentrations of prednisolone.

Cytotoxics:

Increased risk of haematological toxicity with methotrexate.

Diuretics:

Antagonism of diuretic effect; acetazolamide, loop diuretics, and thiazides increased risk of hypokalaemia.

Hormone antagonists:

Aminoglutethimide accelerates metabolism of corticosteroids (reduced effect).

Licorice:

Increased corticosteroid levels.

Mifepristone:

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

Neuromuscular blockers:

Antagonism of the neuromuscular blockade.

Oral Contraceptives:

Alteration in the plasma protein binding and metabolism of prednisolone caused by oestrogens, with or without progesterone, can result in exposure of women to increased levels of unbound prednisolone for prolonged periods of time.

Somatropin:

The growth promoting effect of somatropin may be inhibited.

Sympathomimetics:

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

Theophylline:

increased risk of hypokalaemia.

Ulcer-healing drugs:

Carbenoxolone increases the risk of hypokalaemia.

Vaccines:

Live vaccines should not be given to individuals with impaired immune response as a result of treatment with large doses of corticosteroids.

There is inadequate evidence of safety in human pregnancy. Topical administration of corticosteroids to pregnant animals can cause abnormalities of foetal development including cleft palate and intrauterine growth retardation. There may therefore be a very small risk of such effects in the human foetus. Also, hypoadrenalism may occur in the neonate. 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.

Corticosteroids are excreted in small amounts in breast milk and infants of mothers taking pharmacological doses of steroids should be monitored carefully for signs of adrenal suppression.

None known.

The incidence of predictable undesirable effects, including hypothalamic-pituitary-adrenal (HPA) axis suppression correlates with the relative systemic potency of the drug, dosage, timing of administration and the duration of treatment (see Other Special Warnings and Precautions).

Endocrine/metabolic:

Suppression of the hypothalamic-pituitary-adrenal axis, growth suppression in infancy, childhood and adolescence, menstrual irregularity and amenorrhoea. Cushingoid facies, hirsutism, weight gain, impaired carbohydrate tolerance with increased requirement for antidiabetic therapy. Negative protein and calcium balance. Increased appetite.

Anti-inflammatory and immunosuppressive effects:

Increased susceptibility and severity of infections with suppression of clinical symptoms and signs, opportunistic infections, recurrence of dormant tuberculosis (see Other Special Warnings and Precautions).

Blood and lymphatic system disorders

Alteration in lipid levels (increases in total cholesterol, low density lipoproteins and triglycerides), leukemoid reactions.

Musculoskeletal:

Osteoporosis, vertebral and long bone fractures, avascular osteonecrosis, tendon rupture, proximal myopathy.

Fluid and electrolyte disturbance:

Sodium and water retention, hypertension, potassium loss, hypokalaemic alkalosis.

Neuropsychiatric:

A wide range of psychiatric reactions including affective disorder (such a 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 any may occur in both adults and children. In adults, the frequency of severe reactions has been estimated to the 5-6%. Psychological effects have been reported on withdrawal of corticosteroids; the frequency is unknown.

Psychological dependence. Increased intra-cranial pressure with papilloedema in children (pseudotumour cerebri), usually after treatment withdrawal. Aggravation of epilepsy.

Ophthalmic:

Increased intra-ocular pressure, glaucoma, papilloedema, posterior subcapsular cataracts, corneal or scleral thinning, exacerbation of ophthalmic viral or fungal diseases. Chorioretinopathy.

Cardiac

Myocardial rupture following recent myocardial infarction.

Gastrointestinal:

Nausea, hiccups, dyspepsia, peptic ulceration with perforation and haemorrhage, acute pancreatitis, candidiasis.

Dermatological:

Impaired healing, skin atrophy, bruising, telangiectasia, striae, acne, dermatitis and toxic epidermal necrolysis.

General:

Hypersensitivity including anaphylaxis, has been reported. Leucocytosis. Thrombo-embolism.

Withdrawal symptoms and signs:

Too rapid a reduction of corticosteroid dosage following prolonged treatment can lead to acute adrenal insufficiency, hypotension and in severe cases this could be fatal.

A 'withdrawal syndrome' may also occur including; fever, myalgia, arthralgia, rhinitis, conjunctivitis, painful itchy skin nodules and loss of weight.

Treatment is unlikely to be needed in cases of acute overdosage.

ATC: A07E A01

Prednisolone sodium phosphate is an active corticosteroid with topical anti-inflammatory activity.

Corticosteroids are metabolised mainly in the liver but also in the kidney and are excreted in the urine.

Synthetic corticosteroids such as prednisolone have increased potency when compared with the natural corticosteroids, due to their slower metabolism and lower protein-binding affinity.

None stated.

Witepsol H15.

None known.

2 years.

Store below 25°C.

Fin sealed plastic cavities moulded from 100 micron non-toxic PVC. Each cartoned plastic mould contains 10 suppositories (2 strips of 5 suppositories).

None stated.

UCB Pharma Limited

208 Bath Road

Slough

Berkshire

SL1 3WE

UK

PL 00039/0395

23 February 1993.

March 2008