Predsol suppository and retention enema

MIMS Revision Date: 01 February 2025

1 Name of Medicine

Prednisolone (as sodium phosphate).

2 Qualitative and Quantitative Composition

Predsol suppository contains prednisolone 5 mg (as sodium phosphate).
Predsol retention enema contains prednisolone 20 mg/100 mL (as sodium phosphate).
List of excipients with known effect. Nipastat GL75 which contains methyl hydroxybenzoate, ethyl hydroxybenzoate, propyl hydroxybenzoate, butyl hydroxybenzoate and isobutyl hydroxybenzoate.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Predsol suppository is a white to off white suppository of regular shape with no defects, air occlusion or dirt present.
Predsol retention enema is a clear, colourless liquid free from haze and substantially free from particulate matter.

4 Clinical Particulars

4.1 Therapeutic Indications

Predsol suppository is indicated for the treatment of haemorrhagic and granular proctitis, post-radiation proctitis and rectal complication of Crohn's disease.
Predsol retention enema provides local corticosteroid treatment for rectal and rectosigmoidal disease in ulcerative colitis and Crohn's disease.

4.2 Dose and Method of Administration

Predsol suppository. Administer twice daily, one at bedtime and the other after morning defecation. When response is good, treatment should be continued for some months or, ideally, until sigmoidoscopic or proctoscopic appearances are normal. If symptoms recur, treatment should at once be resumed.
Predsol retention enema. Use one enema nightly on retiring, for two to four weeks. Treatment may be continued in patients showing progressive improvement, but it should not be persisted with if the response has been inadequate. Some patients may relapse after an interval but are likely to respond equally well to a repeated course of treatment. The enema, as packed, is not suitable for use in children.
It may be warmed before administration by placing the bag in a vessel of hot water for a few minutes. Patient must lie down on left side with knees drawn up. Remove the stopper from the bag, lubricate the nozzle with petroleum jelly and gently insert about half the length of the nozzle in the rectum. The bag should then be slowly rolled up like a tube of toothpaste until it is emptied, taking a minute or two to do so. The nozzle should then be removed, with the bag still rolled up, and the whole unit discarded. The patient should then roll over to lie face down for three to five minutes but may sleep in any comfortable position.
Patients should be instructed to discard any unused enema bags 3 months after first opening the outer packaging.

4.3 Contraindications

Hypersensitivity to prednisolone or any of the excipients.
Tuberculous and fungal conditions, acute herpes simplex, vaccinia (cow pox), varicella (chicken pox) and all viral infections.
Traumatised mucosa and/or sepsis in anorectal region.
Concurrent oral or intravenous corticosteroid therapy.
Topical steroid should not be used in patients with markedly impaired circulation, as ulceration in anorectal region may occur.

4.4 Special Warnings and Precautions for Use

For rectal use only. If irritation, rash or rectal bleeding develop Predsol should be discontinued and alternate therapy instituted.
The possibility of systemic absorption of steroids administered via the rectal route is relatively high; therefore, there may be a need for periodic evaluation of hypothalamo-pituitary-adrenal (HPA) - axis suppression by using the urinary free cortisol test or the corticotrophin stimulation test. If the HPA-axis suppression is evident, withdrawal should be attempted and the frequency of application reduced.
Manifestations of adrenal suppression in children include retardation of linear growth, delayed weight gain, low plasma cortisol concentrations and lack of response to corticotrophin stimulation. Manifestations of intracranial hypertension include bulging fontanelles, headache and bilateral papilloedema. Rectal corticosteroid therapy in children should be limited to the minimum amount necessary for therapeutic efficacy; chronic topical corticosteroid therapy may interfere with growth and development.
Drug induced secondary adrenocortical insufficiency may be minimised by gradual reduction in dosage.
If infection in the anorectal region is present, suitable antifungal or antibacterial agents should be used first. If the infection does not respond promptly to therapy, corticosteroid therapy should be discontinued until the infection has been controlled. Corticosteroids may mask the signs of infection.
Caution is required if there is a probability of impending perforation, abscess or other pyrogenic infection or with diverticulitis, active or latent peptic ulcer, renal insufficiency, hypertension, osteoporosis or myasthenia gravis.
There is an enhanced effect of corticosteroids in patients with hypothyroidism and in those with cirrhosis.
Prolonged use of large quantities of rectal corticosteroids may also result in atrophic striae.
Administration of corticosteroids via rectal route should also be used with caution in patients with impaired T-cell function or in those patients receiving other immunosuppressive therapy. The immunosuppressive effects of corticosteroids may be associated with impairment of the normal function of T-cells and macrophages. The result of this impairment may be the activation of latent infection or exacerbation of intercurrent infections, including those caused by Candida, Mycobacterium, Toxoplasma, Strongyloides, Pneumocystis, Cryptococcus, Nocardia and Amoeba.
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.
Use in the elderly. No data available.
Paediatric use. Long-term therapy in infants should be avoided as adrenal suppression may occur. Growth and weight gain changes should be carefully followed and these may result from either the disease or adrenal suppression.
Effects on laboratory tests. Glucocorticoids may decrease ¹³¹I uptake and protein-bound iodine concentrations, making it difficult to monitor the therapeutic response of patients receiving the drugs for thyroiditis. Glucocorticoids may produce false negative results in the nitroblue tetrazolium test for systemic bacterial infection. Glucocorticoids may suppress reactions to skin tests.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Drug interactions may occur if a significant level of prednisolone is systemically absorbed via the rectal route.
The following drug interactions with corticosteroids have been reported for administration of prednisolone by an oral route. These drug interactions with corticosteroids have been selected on the basis of their potential clinical significance: antacids; antidiabetic agents (oral or insulin); digitalis glycosides; diuretics; drugs which induce hepatic microsomal enzymes such as barbiturates, phenytoin and rifampicin; potassium supplements; ritodrine; sodium-containing medications or foods; somatrem or somatropin; vaccines; live viruses or other immunisations.
Drugs that induce hepatic enzymes such as phenobarbital, phenytoin and rifampicin may increase the clearance of corticosteroids and may require increases in corticosteroid dose to achieve the desired response.
Drugs such as troleandomycin and ketoconazole may inhibit the metabolism of corticosteroids and thus decrease their clearance. Therefore, the dose of corticosteroid should be titrated to avoid steroid toxicity. Corticosteroids may increase the clearance of chronic high dose aspirin. This could lead to decreased salicylate serum levels or increase the risk of salicylate toxicity when corticosteroid is withdrawn. Aspirin should be used cautiously in conjunction with corticosteroids in patients suffering from hypoprothrombinemia.
The effect of corticosteroids on oral anticoagulants is variable. There are reports of enhanced as well as diminished effects of anticoagulants when given concurrently with corticosteroids. Therefore, coagulation indices should be monitored to maintain the desired anticoagulant effect.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility. No data available.
Use in pregnancy. (Category A)
Safety of the use of corticosteroids administered via the rectal route in pregnant women has not been established. In vivo studies using pregnant animals have shown that use of large amounts of topical corticosteroids may cause foetal abnormalities. Therefore, topical corticosteroids should be used in pregnancy only when the potential benefits justify the possible risk to the foetus. The drugs should not be used in large amounts or for prolonged periods in pregnant women.
Use in lactation. Prednisolone is excreted into breast milk. Corticosteroids should be used with caution in nursing mothers.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration. However, adverse effects of these medicines include convulsion, vertigo and visual disturbances such as blurred vision which could affect the ability to drive or use machines (see Section 4.8 Adverse Effects (Undesirable Effects)).

4.8 Adverse Effects (Undesirable Effects)

Reporting suspected adverse effects. Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.
Atrophy of the rectal mucosa may occur. Epidermal thinning, telangiectasia, increased fragility of cutaneous blood vessels, purpura and atrophic striae are also reported.
Other adverse dermatological effects of corticosteroids include acneiform eruption; vesiculation; irritation; pruritus; hypertrichosis; rosacea-like eruptions on the face; erythema; hyperesthesia; perioral dermatitis; burning or stinging sensation; folliculitis and hypopigmentation.
Adverse dermatological effects usually improve when the drug is discontinued but may persist for long periods; atrophic striae may be permanent. In addition to the other adverse dermatological effects of corticosteroid therapy, maceration of the skin and miliaria may occur, especially when occlusive dressings are used. Topically applied steroids are generally nonsensitising but allergic contact dermatitis may occur rarely.
Rebound effect may cause dependency on steroids and slowing of healing process.
Rectal corticosteroids should also be used with caution in patients with impaired T-cell function or in those patients receiving other immunosuppressive therapy. The result may be the activation of latent infection or exacerbation of intercurrent infections.
The risk of undesirable local effects increases with prolonged use. Improper use may mask or worsen bacterial, parasitic or viral infections.
The adverse reactions associated with the use of corticosteroids in the large doses necessary to produce a therapeutic response result from excessive action on electrolyte balance; excessive action on other aspects of metabolism including gluconeogenesis; the action on tissue repair and healing; and an inhibitory effect on the secretion of corticotrophin by the anterior pituitary gland. Disturbance of electrolyte and water balance is manifest in sodium retention with oedema and hypertension, and in the increased excretion of potassium with the development of hypokalaemic alkalosis. In extreme cases cardiac failure may be induced. Disturbances of electrolyte balance are common with the naturally occurring corticotrophins, cortisone, deoxycortone and hydrocortisone but are less frequent with the synthetic derivatives prednisone and prednisolone. Other metabolic effects include mobilisation of calcium and phosphorus with osteoporosis and spontaneous fractures; nitrogen depletion and hyperglycaemia with accentuation or precipitation of the diabetic state. The insulin requirements of diabetic patients are increased and appetite is often increased.
The effect on tissue repair manifests as peptic ulceration with haemorrhage and perforation, delayed wound healing and increased liability to infection. Increased susceptibility to all kinds of infection, including sepsis, fungal and viral infection, has been reported.
Large doses of corticosteroids or corticotrophins may produce symptoms typical of hyperactivity of the adrenal cortex, with moonface, buffalo hump, flushing striae and acne sometimes leading to a fully developed Cushing's syndrome. If administration of the hormone is discontinued immediately on the appearance of these symptoms, they are usually reversed but such sudden cessation may be dangerous. The dose of corticosteroid required to cause a decrease or absence of corticotrophin in the blood with consequent atrophy of the adrenal cortex and the time required for its occurrence are very variable. Acute adrenal insufficiency with loss of consciousness may occur during prolonged treatment or on cessation of treatment and may be precipitated by an infection or trauma.
Growth retardation in children has been reported and in this respect cortisone is only one-tenth as potent as prednisone and prednisolone. Other toxic effects include mental and neurological disturbances, intracranial hypertension and, on sudden reduction of dosage during the treatment of rheumatoid arthritis, fatalities attributed to lesions of small arteries and arterioles similar to polyarteritis.
Infections may be masked since corticosteroids have marked anti-inflammatory and antipyretic properties and may produce a feeling of well-being. The administration of corticosteroids may also cause a reduction in the number of circulating lymphocytes. Muscular weakness is an occasional side effect of most corticosteroids, particularly when they are taken in large doses.
Toxic effects occur with all corticosteroid preparations and their incidence rises steeply if dosage increases much above 8 mg daily of oral prednisolone or its equivalent. See Table 1.

4.9 Overdose

If acute ingestion or accidental poisoning occurs, treatment should be symptomatic and supportive. Excessive chronic exposure results in adverse systemic effects. In such cases the use of rectal corticosteroid should be discontinued, with the consideration to tapering dose. Emesis or activated charcoal is not usually indicated unless multiple ingestions are suspected.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

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

5.2 Pharmacokinetic Properties

Absorption. Greater than 20% of a dose may be systemically absorbed when a corticosteroid like prednisolone is administered by a rectal route; the absorption may increase to 50% if the mucosa is inflamed or damaged.
Distribution. Prednisolone is 90 to 95% bound to plasma proteins.
Metabolism. Prednisolone is conjugated in the liver and to some extent in the kidney.
Excretion. Prednisolone is excreted in the urine as free and conjugated metabolites, together with an appreciable proportion of unchanged prednisolone. Prednisolone crosses the placenta and small amounts are excreted in breast milk.

5.3 Preclinical Safety Data

Genotoxicity. No data available.
Carcinogenicity. No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Predsol suppository contains hard fat. There are no preservatives.
Predsol retention enema contains sodium hydroxide, dibasic sodium phosphate heptahydrate, monobasic sodium phosphate, disodium edetate, Nipastat GL75 (preservative) and purified water. Nipastat GL75 contains methyl hydroxybenzoate, ethyl hydroxybenzoate, propyl hydroxybenzoate, butyl hydroxybenzoate and isobutyl hydroxybenzoate.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C. Protect from light.

6.5 Nature and Contents of Container

Predsol suppository: PVC/PVdC/PE blister packs of 10.
Predsol retention enema: Each carton contains seven (7) 100 mL disposable PVC bags with nozzle.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Prednisolone sodium phosphate is a white or slightly yellow hygroscopic crystalline powder or friable granules, odourless or with a slight odour. Prednisolone sodium phosphate 27 mg is approximately equivalent to 20 mg of prednisolone. It is soluble in 1 in 4 of water, 1 in 13 of methyl alcohol, slightly soluble in chloroform and very slightly soluble in acetone. A 0.5% solution in water has a pH of 7.5 to 9.0. Store in airtight containers. Protect from light.
Chemical name: 11β,17,21-trihydroxypregna-1,4-diene- 3,20-dione 21-(disodium phosphate). Molecular formula is C₂₁H₂₇Na₂O₈P and molecular weight is 484.4.
Chemical structure.

CAS number. 125-02-0.

7 Medicine Schedule (Poisons Standard)

Prescription only medicine: S4.

Date of Revision

26 November 2024

Summary Table of Changes