Consumer medicine information

Entocort

Budesonide

BRAND INFORMATION

Brand name

Entocort

Active ingredient

Budesonide

Schedule

What is in this leaflet

This leaflet answers some common questions about Entocort.

It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking Entocort against the benefits they expect it will have for you.

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

Keep this leaflet with your medicine. You may need to read it again.

What ENTOCORT is used for

Entocort is used to treat Crohn's disease. It can be used to treat acute attacks.

Crohn's disease is an inflammatory disease of the bowel. It mainly affects the small bowel and the first part of the large bowel and causes symptoms such as stomach pain, diarrhoea and fever.

Entocort contains budesonide. This belongs to the group of medicines called corticosteroids, which are used to help reduce inflammation in many parts of the body.

Entocort modified release capsules are designed to release their contents gradually in the small bowel and the first part of the large bowel.

Ask your doctor if you have any questions about why Entocort has been prescribed for you. Your doctor may have prescribed it for another reason.

Entocort is not addictive.

Entocort is only available with a doctor's prescription.

This medicine is not expected to affect your ability to drive a car or operate machinery.

Before you take ENTOCORT

When you must not take it

Do not take Entocort if you have an allergy to:

any medicine containing budesonide
any ingredients listed at the end of this leaflet.

Some of the symptoms of an allergic reaction may include:

rash, itching or hives on the skin
shortness of breath, wheezing or difficulty breathing
swelling of the face, lips, tongue or other parts of the body.

Do not give Entocort to children. There is no information available on its use in children.

Do not take this medicine after the expiry date (EXP) printed on the pack or if the packaging is torn or shows signs of tampering. If it has expired or is damaged, return to your pharmacist for disposal.

If you are not sure whether you should start taking this medicine, talk to your doctor or pharmacist.

Before you start to take it

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you have or have had any of the following medical conditions:

any recent infection (including chicken pox and measles)
tuberculosis
diabetes
liver problems
stomach ulcers
brittle bones (osteoporosis)
high blood pressure (hypertension)
eye problems (such as glaucoma or cataracts).

It may not be safe for you to take Entocort if you have any of these conditions.

Tell your doctor if you have NOT had chicken pox or measles. These diseases may be more serious if you get them while taking Entocort. Your doctor may want to vaccinate you for them before you start on Entocort.

Do not take Entocort if you are pregnant, think you might be pregnant or are breastfeeding unless your doctor says to do so. Ask your doctor about the risks and benefits involved. It is not known if it is safe for you to take Entocort while you are pregnant. It may affect your baby.

Like most corticosteroid medicines, it is recommended that you do not breastfeed while taking Entocort as it is found in breast milk.

If you have not told your doctor about any of the above, tell them before you start taking Entocort.

Taking other medicines

Tell your doctor or pharmacist if you are taking any other medicines, including any that you get without a prescription from your pharmacy, supermarket or health food shop.

Some medicines and Entocort may interfere with each other. These include:

other corticosteroid medicines such as tablets, asthma inhalers, nasal sprays, eye/nose drops
medicines used to treat fungal infections (e.g. ketoconazole)
cimetidine, a medicine used to treat reflux and stomach ulcers
medicines for HIV such as cobicistat.

These medicines may be affected by Entocort or may affect how well it works. You may need different amounts of your medicines, or you may need to use different medicines.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking Entocort.

Diagnostic tests for pituitary glands activity may show false low values due to suppression of the adrenal function.

How to take ENTOCORT

Follow all directions given to you by your doctor or pharmacist carefully. They may differ from the information contained in this leaflet.

How much to take

The usual dose is 3 capsules taken once daily in the morning, before breakfast.

How to take it

Swallow Entocort capsules whole with a glass of water.

Do not crush or chew the capsules. If the granules are chewed or crushed they will not work properly.

How long to take it

Continue taking Entocort for as long as your doctor tells you.

A treatment course should normally not exceed 12 weeks.

Entocort should not be stopped suddenly. The dose should be reduced gradually over the last 2-4 weeks.

If you forget to take it

If you miss a dose, take it as soon as you remember, and then go back to taking it as you would normally.

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to.

Do not take a double dose to make up for the dose that you missed. This may increase the chance of you getting an unwanted side effect.

If you are not sure what to do, ask your doctor or pharmacist.

If you have trouble remembering when to take your medicine, ask your pharmacist for some hints.

If you take too much (overdose)

Immediately telephone your doctor, pharmacist, the Poisons Information Centre (131 126) or go to Accident and Emergency at your nearest hospital if you think that you or anyone else may have taken too much Entocort. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

While you are using ENTOCORT

Things you must do

Take Entocort exactly as your doctor has prescribed.

If you have not had chicken pox or measles, avoid close contact with anyone who has these diseases while you are taking Entocort. Tell your doctor straight away if you think that you have been exposed to chicken pox or measles.

Tell your doctor if you have an infection while you are taking Entocort. It may not be safe for you to continue taking Entocort if you have an infection.

If you are about to be started on any new medicine, remind your doctor or pharmacist that you are taking Entocort.

Tell any other doctors, dentists and pharmacists who are treating you that you are taking Entocort.

If you become pregnant while using Entocort, tell your doctor or pharmacist immediately.

Things you must not do

Do not eat grapefruit or drink grapefruit juice while you are taking Entocort. Grapefruit juice, but not other fruit juices, can affect Entocort levels in the body. This may increase the chance of getting unwanted side effects.

Do not stop taking Entocort unless your doctor tells you to. If you need to stop taking Entocort, your doctor will tell you how to do it gradually.

Do not use it to treat any other complaints unless your doctor tells you to.

Do not give this medicine to anyone else.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking Entocort.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side effects.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor or pharmacist if you notice any of the following and they worry you:

indigestion, flatulence
nausea, vomiting, abdominal pain
rapid heart rate or palpitations
headache, dizziness
swelling or rounding of the face, acne, weight gain and bruising more easily
back pain
muscle cramps or muscle weakness (may be due to low levels of potassium in blood)
increased sweating
tiredness
trouble sleeping
tremor, feeling nervous
mood swings
depression, anxiety or aggression
shaking, muscle spasms or twitching
menstrual problems
skin rash, itchiness or discolouration.

These side effects are usually mild.

If your medicine has been changed from other oral corticosteroids (e.g. prednisone, prednisolone or methylprednisolone) to Entocort you may notice some symptoms that bothered you earlier, e.g. rash, or pain in muscles and joints. If this happens or you get headaches, nausea or vomiting, or feel tired please contact your doctor.

Tell your doctor or pharmacist if you notice any of the following:

sign or symptoms of an infection
blurred vision or other visual disturbances.

These may be serious side effects. You may need medical attention.

Tell your doctor immediately or go to Accident and Emergency at your nearest hospital if you notice any of the following:

shortness of breath, wheezing or difficulty breathing
swelling of the face, particularly eyelids, lips, tongue or throat which may cause difficulty in swallowing or breathing
severe rash.

These are very serious side effects. You may need urgent medical attention or hospitalisation. These side effects are very rare.

Tell your doctor or pharmacist if you notice anything else that is making you feel unwell. Other side effects not listed above may occur in some patients.

If you have changed from or used high doses of oral corticosteroids over a long period of time, your adrenal glands may be affected. Your doctor may do tests to check how the adrenal glands are working.

Your doctor may also tell you to take additional oral corticosteroids during periods of stress such as trauma and surgery.

A slowing of the rate of growth maybe observed if Entocort is used in children and adolescents.

Ask your doctor to answer any questions you may have.

After using ENTOCORT

Storage

Keep your Entocort capsules in the bottle until it is time to take them.

Replace the cap firmly after use. If you take Entocort out of the bottle it will not keep well.

Keep Entocort in a cool dry place where the temperature stays below 30°C.

Do not store Entocort or any other medicine in the bathroom or near a sink. Do not leave it on a window sill or in the car. Heat and dampness can destroy some medicines.

Keep it where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

If your doctor tells you to stop taking Entocort or it has passed its expiry date, ask your pharmacist what to do with any capsules you have left over.

Product description

What it looks like

Entocort modified release capsules are two-piece hard gelatin capsules, size 1 with an opaque light grey body and an opaque pink cap. The cap has black print CIR 3mg.

Entocort is supplied in bottles containing 90 capsules.

Ingredients

Each Entocort modified release capsule contains 3 mg of budesonide as the active ingredient.

The capsules also contain the following inactive ingredients:

ethylcellulose
tributyl acetylcitrate
methacrylic acid copolymer
triethyl citrate
dimeticone 1000
polysorbate 80
purified talc
Sugar Spheres (ARTG No. 2535).

Each capsule shell is made from gelatin, titanium dioxide, iron oxide black, iron oxide red, iron oxide yellow, colloidal anhydrous silica, liquid paraffin and sodium lauryl sulfate.

The capsules are printed with TekPrint SW-9008 Black Ink (ARTG PI No. 2328).

Supplier

Chiesi Australia Pty Ltd
Suite 3, 22 Gillman Street
Hawthorn East, VIC 3123
Email: [email protected]
Website: www.chiesi.com.au

This leaflet was prepared in January 2023.

Australian Registration Number:
AUST R 62812

Published by MIMS February 2023

BRAND INFORMATION

Brand name

Entocort

Active ingredient

Budesonide

Schedule

1 Name of Medicine

Budesonide.

2 Qualitative and Quantitative Composition

Entocort contains 3 mg of budesonide and is a hard gelatin capsule filled with gastric acid resistant, prolonged release granules for oral use. The granules are practically insoluble in gastric juice and have prolonged release properties adjusted to release budesonide in the ileum and the ascending colon.

Excipients with known effect.

Sugars.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Entocort 3 mg modified release capsules are two-piece hard gelatin capsule, size 1 with an opaque light grey body and an opaque pink cap. The cap has black print CIR 3 mg.

4 Clinical Particulars

4.1 Therapeutic Indications

Entocort modified release capsules are indicated for the induction of remission in adult patients with mild to moderate Crohn's disease affecting the ileum and/or the ascending colon.

4.2 Dose and Method of Administration

Dosage.

Adults.

The recommended daily dose for induction of remission is 9 mg, administered once daily in the morning. The dose should be taken before meals.
When treatment with Entocort modified release capsules is to be discontinued, the dose should be tapered over the last 2 to 4 weeks of therapy and not stopped abruptly. The total duration of therapy should be no more than 12 weeks in any single course.

Children.

There is presently no experience with Entocort modified release capsules in children.

Elderly.

No special dose adjustment is recommended. However, experience with Entocort modified release capsules in the elderly is limited.

Method of administration.

The modified release capsules should be swallowed whole with water. The modified release capsules must not be chewed.

4.3 Contraindications

Systemic or local bacterial, fungal or viral infections.
Hypersensitivity to any of the ingredients listed in Section 6.1 List of Excipients.

4.4 Special Warnings and Precautions for Use

Identified precautions.

Caution should be taken in patients with tuberculosis, hypertension, diabetes mellitus, osteoporosis, peptic ulcer, glaucoma or cataracts, or with a family history of diabetes or glaucoma, or with any other condition where glucocorticosteroids may have unwanted effects.

Transferring from systemic glucocorticosteroids.

During transfer from conventional systemic steroid therapy to Entocort, symptoms related to the change in systemic steroid dose may occur e.g. allergic symptoms such as rhinitis and eczema may recur.
Particular care is needed in patients who are transferred from systemic glucocorticoid treatment with higher systemic effect to Entocort. These patients may have adrenocortical suppression. Therefore, monitoring of adrenocortical function may be considered in these patients and their dose of systemic steroid should be reduced cautiously.

Viral infections.

Chickenpox and measles can have a more serious course in patients on oral glucocorticosteroids. In patients who have not had these diseases, particular care should be taken to avoid exposure. If exposed, therapy with varicella zoster immune globulin (VZIG) or pooled intravenous immunoglobulin (IVIG), as appropriate, may be indicated. If chickenpox develops, treatment with antiviral agents may be considered.

HPA axis suppression and adrenal insufficiency.

As with all glucocorticosteroids, some degree of adrenal suppression may occur in particularly sensitive patients, therefore, monitoring of haematological and adrenal function is strongly advised and patients should be instructed to carry an appropriate warning card.
In situations where patients are subject to surgery or other stress situations, supplementation with a systemic glucocorticosteroid is recommended.

Discontinuation.

Some patients may feel unwell in a non-specific way during the withdrawal phase, e.g. pain in muscles and joints. A general insufficient glucocorticosteroid effect should be suspected if, in rare cases, symptoms such as tiredness, headache, nausea and vomiting may occur. In these cases, a temporary increase in the dose of systemic glucocorticosteroids is sometimes necessary.

CYP3A interactions.

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 (also see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Chronic use.

When Entocort capsules are used chronically in excessive doses, systemic glucocorticosteroid effects such as hypercorticism and adrenal suppression may appear.

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. See Section 4.8 Adverse Effects (Undesirable Effects).

Gastrointestinal tolerance.

The toxicity of Entocort, with focus on the gastrointestinal tract, has been studied in cynomolgus monkeys in doses up to 5 mg/kg (≥ 25 times the recommended daily dose in man) after repeated oral administration for up to 6 months. No effects were observed in the gastrointestinal tract, either at gross pathology or in the histopathological examination.

Excipients.

Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.
This medicine contains less than 1 mmol sodium (23 mg) per dosage unit. It is essentially sodium-free.

Use in hepatic impairment.

Compromised hepatic function has an influence on the pharmacokinetics of budesonide with a reduced elimination rate and an increased oral systemic availability.

Use in the elderly.

See Section 4.2 Dose and Method of Administration; Section 4.4 Special Warnings and Precautions for Use.

Paediatric use.

See Section 4.2 Dose and Method of Administration; Section 4.4 Special Warnings and Precautions for Use.

Effects on laboratory tests.

See Section 4.5 Interactions with Other Medicines and Other Forms of Interactions.

4.5 Interactions with Other Medicines and Other Forms of Interactions

The metabolism of budesonide is primarily mediated by CYP3A4, a subfamily of cytochrome P450. Inhibition of this enzyme can therefore increase systemic exposure of budesonide. During concomitant administration of drugs which are potent CYP3A4 inhibitors (such as ketoconazole), plasma concentrations of budesonide can be significantly higher than observed in patients in clinical trials. As a consequence of this, lower doses of Entocort should be considered.

Ketoconazole.

The kinetic properties of budesonide were investigated in healthy subjects with or without ketoconazole 200 mg daily. The mean AUC for budesonide was 31.6 nanomol.h/L, after administration of ketoconazole for three consecutive days this increased to 238.2 nanomol.h/L. The relative systemic availability increased 7-fold. If concomitant treatment of ketoconazole and oral budesonide is indicated, the dose of budesonide should be reduced if systemic glucocorticoid side effects occur.

Grapefruit juice.

The systemic exposure for oral budesonide increases about two times after the intake of grapefruit juice. As with other drugs primarily metabolised through CYP3A4, regular ingestion of grapefruit or grapefruit juice should be avoided with budesonide administration.

Cimetidine.

The kinetics of budesonide were investigated in healthy subjects with or without cimetidine, 1000 mg daily. After a 4 mg oral dose of budesonide the values of C_max with and without cimetidine were 5.1 and 3.3 nanomol/L. The corresponding values for systemic availability of budesonide were 12 and 10%, respectively. This indicated a slight inhibitory effect on hepatic metabolism of budesonide, caused by cimetidine. This should be of little clinical importance.

Other interactions.

No other data have been reported regarding interactions between budesonide and other drugs in patients with Crohn's disease.
Because adrenal function may be suppressed, an ACTH stimulation test for diagnosing pituitary insufficiency might show false results (low values).

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category B3)
In animal studies, budesonide was found to cross the placental barrier.
In pregnant animals, administration of budesonide, like other glucocorticosteroids, is associated with abnormalities of fetal development and fetal adrenal suppression. The relevance of this finding to humans has not been established.
However, as with other drugs the administration of Entocort during pregnancy requires that the benefits for the mother are weighed against the risks for the fetus.
Budesonide is excreted in breast milk. Due to the low systemic bioavailability of oral budesonide (see Section 5.2 Pharmacokinetic Properties), the amount of drug present in the breast milk is likely to be low, depending on the dose given. However, there are no study data on the use of oral budesonide by nursing mothers or their infants. Therefore, a decision should be made whether to discontinue breastfeeding or to discontinue Entocort, taking into account the clinical importance of Entocort to the mothers and the given dose.

4.7 Effects on Ability to Drive and Use Machines

Entocort has no or negligible influence on the ability to drive and use machines.

4.8 Adverse Effects (Undesirable Effects)

Clinical studies.

Entocort is generally well tolerated. In clinical studies most adverse events were of mild to moderate intensity and of a non-serious character.
Data from three controlled clinical trials including Entocort 9 mg (n=268), prednisolone 40 mg (n=145) and placebo (n=66) showed no statistically significant differences in frequency for any adverse events when comparing the Entocort 9 mg group and placebo (see Table 1).

Data from the three controlled clinical trials showed statistically that the relative risk of glucocorticosteroid side effects with Entocort 9 mg is reduced compared to prednisolone 40 mg on an overall basis, and in particular with respect to moon face, acne and buffalo hump. The relative risk for glucocorticoid adverse event, particularly occurrence of moon face, was increased relative to placebo.

Tabulated list of adverse reactions.

The following suspected adverse reactions is based on clinical trials and/or spontaneous post-marketing reports.
The following definitions apply to the incidence of undesirable effects: 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 estimate from the available data). See Table 2.

Description of selected adverse reactions.

Side effects typical of systemic glucocorticosteroids (Cushingoid features), reduced growth velocity and adrenal suppression may occur. These side effects are dependent on dose, treatment time, concomitant and previous glucocorticosteroid intake and individual sensibility.
Long term experience with Entocort is limited. Although not reported during short term trials Entocort, the possible occurrence of adverse effects typical of glucocorticosteroids, such as osteoporosis, diabetes, cataracts must be considered.

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 http://www.tga.gov.au/reporting-problems.

4.9 Overdose

Acute overdosage with Entocort, even in excessive doses, is not expected to be a clinical problem. When used chronically in excessive doses systemic corticosteroid effects such as hypercorticism and adrenal suppression as well as osteoporosis may appear. If such changes occur the dosage of Entocort should be discontinued consistent with accepted procedures for discontinuing prolonged oral therapy with systemic steroids.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Studies in animals and humans have shown an advantageous ratio between topical anti-inflammatory activity and systemic glucocorticoid effect over a wide dose range. This is explained by the extensive first-pass hepatic degradation of budesonide after systemic absorption, approximately 85-90%, in combination with the low potency of formed metabolites. The exact mechanism of action of budesonide in the treatment of Crohn's disease is not fully understood. Anti-inflammatory actions, such as blocking the inflammatory cell influx and inhibition of inflammatory mediator release by inhibition of the arachidonic acid pathway, are probably important. The intrinsic potency of budesonide, measured as affinity to the glucocorticoid receptor, is about 15 times higher than that of prednisolone.
Entocort modified release capsules 9 mg have been shown in clinical pharmacology studies and controlled clinical trials to have equal efficacy, but less effect on the hypothalamus-pituitary-adrenal (HPA) axis and inflammatory markers than prednisolone 40 mg in the treatment of Crohn's disease.
Entocort in studies of up to 8 weeks produced a dose dependent suppression of morning plasma cortisol, on 24-hour plasma cortisol (AUC 0-24 h) and on 24-hour urine cortisol, however, at the recommended dose of 9 mg once daily this effect was significantly less than that seen with prednisolone 20-40 mg daily. ACTH tests have shown that Entocort, compared with prednisolone, have less impact on adrenal function. In one study, adrenal dysfunction, as measured by short ACTH test, was seen in 58% of patients on 9 mg Entocort versus 84% on 40 mg prednisolone. The long-term effect of Entocort on bone density and growth has not been studied in patients with Crohn's disease. In a 5 day study in healthy volunteers, 9 mg and 15 mg doses of Entocort were shown to have a similar suppressant effect on osteocalcin levels as 20 mg prednisolone.

Clinical trials.

A dose-finding study (n = 258) conducted over 12 weeks demonstrated that the lowest effective dose for inducing remission in active ileal or ileocaecal Crohn's disease with budesonide was 9 mg. The recommended dosage of 9 mg once daily has been compared with prednisolone 40 mg for the efficacy of inducing remission in two other studies of equal size (n = 176 and 177, respectively). In one study, Entocort was significantly slower at inducing remission with a median time of 29 days to remission compared to 16 days for prednisolone 40 mg. Another study showed Entocort was faster at reaching remission compared to prednisolone, with a median time of 17 days for Entocort 9 mg and 28 days for prednisolone 40 mg. The percentage of patients in remission after 8 weeks' treatment showed no statistically significant differences in either of the two studies. In one study the remission rate in the Entocort group was 52% compared with 65% for prednisolone, while in the other study the remission rate in both groups was 60%. The overall incidence of glucocorticosteroid associated side effects was statistically significantly lower with Entocort. In one study (n = 178) the incidence of glucocorticosteroid side effects was 50% for 9 mg Entocort and 59% for 40 mg prednisolone. In another study (n = 176) the corresponding figures were 33% for 9 mg Entocort and 55% for 40 mg prednisolone.
No clinical studies have been conducted in children or the elderly.

5.2 Pharmacokinetic Properties

Absorption.

After oral dosing of plain micronised budesonide, absorption is rapid and seems to be complete. Following oral dosing of Entocort modified release capsules 9 mg, taken immediately before breakfast, mean maximum plasma concentration is approximately 5-10 nanomol/L (C_max) at 3-5 hours (T_max). Systemic availability in healthy subjects is approximately 10%, the same as after oral dosing of plain micronised budesonide, which indicates absorption is complete.
While Entocort modified release capsules have equivalent systemic absorption to plain budesonide capsules, it has a longer T_max, due to its gastric-acid resistant, prolonged release properties. In a pharmacokinetic study in healthy volunteers, the absorption of budesonide in the targeted area, the ileum and ascending colon, was 58% and 34%, respectively, for Entocort modified release capsules and capsules containing plain budesonide. Terminal ileal and ascending colon absorption in patients with Crohn's disease was more variable (range 3-84%; mean 42.5%).
Following a single dose of Entocort modified release capsules in patients with active Crohn's disease, systemic availability is about 20%. After repeated dosing for 8 weeks, the systemic availability decreases but remains above that seen in healthy subjects.

Distribution.

The volume of distribution of budesonide in adult man is approximately 3 L/kg indicating a high tissue affinity. Plasma protein binding averages 85-90% in humans.

Metabolism.

Budesonide is extensively biotransformed by first-pass hepatic degradation (~90% in man) to more polar metabolites of low glucocorticosteroid potency. The glucocorticosteroid activity of the major metabolites, 6β-hydroxybudesonide and 16α-hydroxy-prednisolone, is less than 1% of that of budesonide.

Excretion.

Excretion of budesonide given as Entocort modified release capsules is rate limited by its absorption, and the terminal half-life averages 4 hours.

5.3 Preclinical Safety Data

Genotoxicity.

The mutagenic potential of budesonide was evaluated in 6 different test systems. No mutagenic or clastogenic effects of budesonide were found.

Carcinogenicity.

The carcinogenic potential of budesonide has been evaluated in mouse and rat at oral doses up to 200 and 50 microgram/kg/day, respectively. No oncogenic effect was noted in the mouse. One study indicated an increased incidence of brain gliomas in male Sprague-Dawley rats given budesonide, however the results were considered equivocal. Further studies performed in male Sprague-Dawley and Fischer rats showed that the incidence of gliomas in the budesonide treated rats was low and did not differ from that in the reference glucocorticoid groups or the controls. It has been concluded that treatment with budesonide does not increase the incidence of brain tumours in the rat.
In male rats dosed with 10, 25 and 50 microgram/kg/day, those receiving 25 and 50 microgram/kg/day showed an increased incidence of primary hepatocellular tumours. This was observed in all three steroid groups (budesonide, prednisolone, triamcinolone acetonide) in a repeat study in male Sprague-Dawley rats thus indicating a class effect of corticosteroids.

6 Pharmaceutical Particulars

6.1 List of Excipients

The excipients are ethylcellulose, tributyl acetylcitrate, methacrylic acid copolymer, triethyl citrate, dimeticone 1000, polysorbate 80, purified talc and Sugar Spheres (ARTG PI No: 2535).
The capsule shell is made from gelatin, titanium dioxide, iron oxide black, iron oxide red, iron oxide yellow, colloidal anhydrous silica, liquid paraffin and sodium lauryl sulfate.
The capsules are printed with TekPrint SW-9008 Black Ink (ARTG PI No. 2328).

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 Therapeutics Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 30°C. Replace the cap firmly after use.

6.5 Nature and Contents of Container

A pack of 90 modified release capsules are provided in a high-density polyethylene bottle, with a polypropylene screw cap including a desiccant. The modified release capsules should be dispensed and stored in the original container.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with the local requirements.

6.7 Physicochemical Properties

Budesonide is a white to off white powder, freely soluble in chloroform, sparingly soluble in ethanol and practically insoluble in water and heptane. Budesonide is a mixture of two epimeric forms, epimer A and epimer B, in a 50:50 ratio. The epimer mixture melts with decomposition between 224°C and 231.5°C.
The active ingredient, budesonide, is a non-halogenated glucocorticoid structurally related to 16α hydroxyprednisolone. The chemical name is 16α, 17α-22R, S- propylmethylenedioxy-pregna-1,4-diene-11β, 21-diol-3, 20-dione.

Chemical structure.

Budesonide.

CAS number.

51333-22-3.

7 Medicine Schedule (Poisons Standard)

Prescription only medicine (Schedule 4).

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Entocort

Budesonide

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BRAND INFORMATION

Entocort 3 mg