Consumer medicine information

Budenofalk Enteric Capsules

Budesonide

BRAND INFORMATION

Brand name

Budenofalk

Active ingredient

Budesonide

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Budenofalk Enteric Capsules.

SUMMARY CMI

BUDENOFALK® capsules

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I taking BUDENOFALK Capsules?

BUDENOFALK capsules contain the active ingredient, budesonide. BUDENOFALK capsules are used to treat Crohn's disease affecting the ileum and/or the ascending colon (inflammation of the last section of the small bowel and/or the first section of the large bowel) for 8 weeks.

For more information, see Section 1. Why am I taking BUDENOFALK Capsules? in the full CMI.

2. What should I know before I take BUDENOFALK Capsules?

Do not take if you have ever had an allergic reaction to BUDENOFALK capsules or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I take BUDENOFALK Capsules? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with BUDENOFALK capsules and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I take BUDENOFALK Capsules?

  • The recommended dose is one BUDENOFALK capsule three times a day (morning, midday and evening), or three BUDENOFALK capsules once daily in the morning.
  • This medicine may only be used orally.

More instructions can be found in Section 4. How do I take BUDENOFALK Capsules? in the full CMI.

5. What should I know while taking BUDENOFALK Capsules?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are taking BUDENOFALK capsules.
  • If you become pregnant while taking this medicine, tell your doctor immediately.
Things you should not do
  • Do not take BUDENOFALK capsules to treat any other complaints unless your doctor tells you to.
  • Do not give your medicine to anyone else, even if they have the same condition as you.
  • Do not stop taking BUDENOFALK capsules or change the dosage without checking with your doctor.
Driving or using machines
  • This medicine is not expected to affect your ability to drive a car or operate machinery.
Looking after your medicine
  • Keep BUDENOFALK capsules in their original packaging until it is time to take them.
  • Keep your capsules in a cool and dry place where the temperature stays below 30°C.
  • 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.

For more information, see Section 5. What should I know while taking BUDENOFALK Capsules? in the full CMI.

6. Are there any side effects?

All medicines can have side effects. If they do occur, they are usually minor and temporary. The most common side effects taking BUDENOFALK capsules are: abdominal pain, pain in the upper middle part of the abdomen, diarrhoea / soft stools, high blood pressure, acne, tiredness, general feeling of being ill.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

BUDENOFALK® capsules

Active ingredient: budesonide

Consumer Medicine Information (CMI)

This leaflet provides important information about taking BUDENOFALK capsules. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about taking BUDENOFALK capsules.

Where to find information in this leaflet:

1. Why am I taking BUDENOFALK capsules?
2. What should I know before I take BUDENOFALK capsules?
3. What if I am taking other medicines?
4. How do I take BUDENOFALK capsules?
5. What should I know while taking BUDENOFALK capsules?
6. Are there any side effects?
7. Product details

1. Why am I taking BUDENOFALK capsules?

BUDENOFALK capsules contain the active ingredient, budesonide distributed within enteric-coated (gastric resistant) granules. Budesonide belongs to a group of medications called corticosteroids.

BUDENOFALK capsules are used to treat Crohn's disease affecting the ileum and/or the ascending colon (inflammation of the last section of the small bowel and/or the first section of the large bowel) for 8 weeks.

2. What should I know before I take BUDENOFALK capsules?

Warnings

Do not take BUDENOFALK capsules if:

  • you are allergic to budesonide, or any of the ingredients listed at the end of this leaflet.
  • Always check the ingredients to make sure you can use this medicine.
  • Do not take this medicine if you suffer from a severe liver disease (liver cirrhosis).
  • Do not take this medicine after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering.

Check with your doctor if you:

  • have any other conditions and taking medicines
    - liver disease
    - lung disease (tuberculosis)
    - high blood pressure
    - diabetes, when the level of sugar in the blood is too high
    - disease which causes bones to become less dense, gradually making them weaker, more brittle and likely to break (osteoporosis)
    - ulcer in stomach or duodenum
    - glaucoma (high pressure in the eye)
    - cataracts
    - family history of diabetes or glaucoma
    - any infections
    - any stresses
    - intolerance to sugars
    - any other disease where use of steroids may have unwanted effects.
  • have an infection. The symptoms of some infections can be atypical or less pronounced.
  • have been exposed to chicken pox, measles and shingles infections. These illnesses may become more severe when you take BUDENOFALK capsules.
  • have not yet had measles.
  • need to be vaccinated, please speak to your doctor first.
  • know you are due to have an operation, please tell your doctor that you are taking BUDENOFALK capsules.
  • have been treated with a stronger corticosteroid preparation before starting treatment with BUDENOFALK capsules, your symptoms may reappear when the medicine is changed. If this happens, contact your doctor.
  • experience blurred vision or other visual disturbances.

BUDENOFALK capsules are not recommended for use in children or adolescents.

BUDENOFALK capsules contain lactose and sucrose. This may cause a problem if you have intolerance to some sugars.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

Your doctor will discuss the risks and benefits of taking BUDENOFALK capsules if you are pregnant or breastfeeding.

3. What if I am taking other medicines?

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

Some medicines may interfere with BUDENOFALK capsules and affect how it works.

  • cardiac glycosides such as digoxin, medicines used to treat heart conditions
  • diuretics, medicines used to treat excess fluid in your body
  • ketoconazole and itraconazole, medicines used to treat fungal infections
  • antibiotics such as clarithromycin, medicines used to treat infections
  • ritonavir and cobicistat medicines used to treat HIV infections
  • carbamazepine, medicine used to treat epilepsy
  • rifampicin, medicine used to treat tuberculosis
  • contraceptive pill
  • cholestyramine, medicine used to reduce cholesterol level
  • cimetidine, medicine used to reduce stomach acid.

These medicines may be affected by BUDENOFALK capsules or they may affect how well BUDENOFALK capsules work. You may need different doses of your medicine(s) or you may need to take different medicines. Your doctor or pharmacist will advise you if this is required.

Avoid drinking grapefruit juice while you are taking BUDENOFALK capsules as this can alter its effects.

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

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect BUDENOFALK capsules.

4. How do I take BUDENOFALK capsules?

Follow all directions given to you by your doctor or pharmacist carefully.

How much to take

  • Adults and the elderly:
    One BUDENOFALK capsule three times a day (morning, midday and evening), or three BUDENOFALK capsules once daily in the morning.

BUDENOFALK capsules treatment should be terminated by gradual reduction of your dose over the last two weeks. The dosage should be reduced to two capsules daily (one in the morning and one in the evening) for one week. In the last week, only one capsule should be taken in the morning.

Once you have started taking BUDENOFALK capsules, do not stop taking it abruptly.

When to take

Take BUDENOFALK capsules about 30 minutes before a meal.

Take your medicine at about the same time each day.

Taking it at the same time each day will have the best effect. It will also help you remember when to take it.

How to take

Swallow the capsules whole with a glass of water. Do not chew or crush the capsules.

If you have difficulty swallowing the capsules, open the capsule and take the granules with plenty of liquid. Do not chew or crush the granules.

Due to the gastro-resistant coating being on the granules rather than the capsules, there is no change in how the medicine works by swallowing the capsules whole versus opening the capsules and swallowing the granules directly.

How long to take

Your doctor will decide how long you need to continue the treatment with this medicine. This will depend on your condition. BUDENOFALK capsules may be used for up to 8 weeks for each episode of Crohn's disease.

If you forget to take

Take your dose as soon as you remember and continue to take 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.

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

If you think that you have taken too many BUDENOFALK capsules no emergency treatment is required. If you have any concerns, you should

  • contact your doctor, or
  • phone the Poisons Information Centre
    (by calling 13 11 26), or

5. What should I know while taking BUDENOFALK capsules?

Things you should do

If you are about to start on any new medicine, remind your doctor and pharmacist that you are taking BUDENOFALK capsules.

Tell any other doctors, dentists, and pharmacists who treat you that you are taking BUDENOFALK capsules.

If you are going to have surgery, tell the surgeon or anaesthetist that you are taking BUDENOFALK capsules.

It may affect other medicines used during surgery.

If you become pregnant while taking BUDENOFALK capsules, tell your doctor immediately.

Things you should not do

Do not take BUDENOFALK capsules to treat any other complaints unless your doctor tells you to.

Do not give your medicine to anyone else, even if they have the same condition as you.

Do not stop taking BUDENOFALK capsules or change the dosage without checking with your doctor.

Driving or using machines

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

Looking after your medicine

Keep BUDENOFALK capsules in their original packaging until it is time to take them.

Keep your BUDENOFALK capsules in a cool and dry place where the temperature stays below 30°C.

Do not store it 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.

Getting rid of any unwanted medicine

If you no longer need to take this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not take this medicine after the expiry date.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, speak to your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effectsWhat to do
When using BUDENOFALK capsules:
  • abdominal pain
  • pain in the upper middle part of the abdomen
  • diarrhoea / soft stools
  • high blood pressure
  • acne
  • tiredness, general feeling of being ill.
Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effect

Serious side effectsWhat to do
  • signs or symptoms of an infection
  • headache
  • changes in behaviour such as depression, irritability, euphoria, restlessness, anxiety or aggression.
Call your doctor or pharmacist immediately if you notice any of these symptoms.
Symptoms of allergic reaction:
  • swelling of the limbs, face, lips, mouth or throat which may cause difficulty swallowing or breathing
Call your doctor immediately or go straight to the Emergency Department at your nearest hospital if you notice any of these symptoms.

The following side effects have been reported with medicines which are in the same class as BUDENOFALK capsules (corticosteroids). These side effects listed below depend on the dose, the period of treatment, whether there has been prior or accompanying treatment with other corticosteroid preparations and on the individual sensitivity.

Possible class effects are:

  • Cushing Syndrome: roundness of the face, weight gain, increased risk of high blood sugar, fluid retention, reduced growth
  • increased risk of infection
  • irregular periods in women, male hair growth patterns in women, impotence
  • mood changes such as depression, irritation or euphoria
  • blurred vision (e.g. glaucoma and cataract)
  • increased risk of blood clotting, disease of the blood vessels (associated with stopping steroid use after long term therapy)
  • stomach complaints, gastric ulcers, pancreatitis and constipation
  • muscle pain and bone weakness (osteoporosis), loss of bone and cartilage (aseptic bone necrosis)
  • rash from hypersensitivity reactions (allergic exanthema), formation of red stripes (striations) and bleeding in the skin, delayed wound healing, local skin reactions (such as contact dermatitis)
  • isolated cases: increased brain pressure with possible additional swelling of the optic disk in adolescents.

These side effects are typical for systemic corticosteroids, such as prednisolone. Data shows that the frequency of systemic adverse reactions is lower with BUDENOFALK capsules.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects that you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What BUDENOFALK capsules contain

Active ingredient
(main ingredient)		Budesonide 3 mg
Other ingredients
(inactive ingredients)		lactose monohydrate
sugar spheres (sucrose)
triethyl citrate
purified talc
povidone
methacrylic acid copolymer
ammonio methacrylate copolymer
gelatin
sodium lauryl sulphate
titanium dioxide
iron oxide red
iron oxide black
erythrosine.

Do not take this medicine if you are allergic to any of these ingredients.

What BUDENOFALK capsules looks like

BUDENOFALK capsules are pink opaque capsules containing round white pellets.

BUDENOFALK capsules are approved in blister packs of 9 and 10 (starter packs), 50 and 90.

Who distributes BUDENOFALK capsules

Dr Falk Pharma Australia Pty Ltd,
9 Help Street
Chatswood NSW 2067

Australian Registration Number: AUST R 179566

BUDENOFALK® is a registered trademark of Dr. Falk Pharma GmbH, Germany.

This leaflet was revised in November 2024.

Published by MIMS May 2025

BRAND INFORMATION

Brand name

Budenofalk

Active ingredient

Budesonide

Schedule

S4

 

1 Name of Medicine

Budenofalk capsules.
Budesonide.

2 Qualitative and Quantitative Composition

Budenofalk capsules contain 3 mg of budesonide within enteric-coated (gastro-resistant) granules as the active ingredient.

Excipients of known effect.

Sugars (as lactose monohydrate and sucrose).
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Budenofalk capsules are presented as pink opaque, oblong hard gelatin capsules.

4 Clinical Particulars

4.1 Therapeutic Indications

Budenofalk enteric capsules are indicated for:
Induction of remission in patients with mild to moderately active Crohn's disease affecting the ileum and/or the ascending colon (see Section 5.1 Pharmacodynamic Properties, Clinical trials).

4.2 Dose and Method of Administration

Adults and the elderly.

For acute Crohn's disease (for 8 weeks):
9 mg budesonide once daily in the morning, or
3 mg budesonide 3 times daily (morning, midday and evening).
Safety and efficacy of Budenofalk capsules have been assessed for up to 8 weeks in adults. Continuous treatment beyond 8 weeks is not recommended. Patients may receive episodic treatment.

At discontinuation.

At the end of treatment, the dosage should be tapered gradually, to avoid the possibility of insufficient function of the cortex of the suprarenal gland.
In the first week of tapering, the dosage should be reduced to two capsules daily, one in the morning, one in the evening. In the second week of tapering, only one capsule should be taken in the morning. After two weeks of gradual dose reduction, treatment can be discontinued.

Method of administration.

The Budenofalk capsules may be taken whole, without chewing or crushing, about 30 minutes before meals with sufficient water. Patients with difficulty swallowing the capsules may open the capsule and administer the enteric-coated granules without chewing or crushing and with plenty of liquid.
Due to the enteric coating on the granules inside the Budenofalk capsules and not on the capsule shell itself, the dissolution of budesonide is unchanged whether the patient administers the capsule whole or opens the capsules and then swallows the granules.
Furthermore, there are no data on the effects of crushing the granules before dosing on the pharmacokinetics of budesonide nor on the safety and efficacy of the compound and is therefore not recommended.

4.3 Contraindications

Budenofalk capsules are contraindicated in patients with the following:
hypersensitivity to budesonide or any of the ingredients;
hepatic cirrhosis.

4.4 Special Warnings and Precautions for Use

Treatment with Budenofalk capsules does not appear useful in patients with Crohn's disease affecting the upper gastro-intestinal tract. Extraintestinal symptoms, e.g. involving the skin, eyes or joints, are unlikely to respond to Budenofalk capsules because of its local action.
Treatment with Budenofalk capsules results in lower systemic glucocorticoid levels than systemic glucocorticoid therapy. Particular care is needed in patients who are transferred from systemically acting glucocorticoid treatment with higher systemic effect to Budenofalk capsules. These patients may have adrenocortical suppression at the time of initiation of treatment with Budenofalk capsules. Therefore, monitoring of adrenocortical function may be considered in these patients and their dose of systemic glucocorticoid should be reduced cautiously.
Caution is required in patients with tuberculosis, hypertension, diabetes mellitus, osteoporosis, peptic ulcer, glaucoma, cataracts, family history of diabetes, family history of glaucoma, or any other condition in which glucocorticoids may have undesirable effects.
Systemic effects of glucocorticoids may occur, particularly when prescribed at high doses, for prolonged periods and for those agents which are highly absorbed systemically. Such effects may include Cushing syndrome, adrenal suppression, growth retardation, decreased bone mineral density, cataract, glaucoma and a wide range of psychiatric/ behavioural effects (see Section 4.8 Adverse Effects (Undesirable Effects)).
Glucocorticoids may cause suppression of the HPA axis and reduce the stress response. When patients are subject to surgery or other stresses, supplementary systemic glucocorticoid treatment is recommended.
As with all glucocorticoids, some degree of adrenal suppression may occur in particularly sensitive patients, therefore, monitoring of haematological and adrenal function is strongly advised.

Infection.

Suppression of the inflammatory response and immune function increases the susceptibility to infections and their severity. The risk of deterioration of bacterial, fungal, amoebic and viral infections during glucocorticoid treatment should be carefully considered. The clinical presentation may often be atypical and serious infections such as septicaemia and tuberculosis may be masked, and therefore may reach an advanced stage before being recognised.

Chickenpox.

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. If the patient is a child, parents must be given the above advice. Passive immunisation with varicella zoster immunoglobulin (VZIG) is needed by exposed non-immune patients who are receiving systemic glucocorticoids 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. Glucocorticoids should not be stopped and the dose may need to be increased.

Measles.

Patients with compromised immunity who have come into contact with measles should, wherever possible, receive normal immunoglobulin as soon as possible after exposure.

Live vaccines.

Live vaccines should not be given to individuals with chronic corticosteroid use. The antibody response to other vaccines may be diminished.

Visual disturbance.

Visual disturbance may be reported with systemic and topical glucocorticoid 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 glucocorticoids.

Others.

Budenofalk capsules contain lactose and sucrose. Patients with rare hereditary problems of galactose or fructose intolerance, glucose-galactose malabsorption, sucrase-isomaltase insufficiency, the Lapp lactase deficiency or the congenital lactase deficiency should not take this medicine.
Concomitant treatment with ketoconazole or other CYP3A4 inhibitors should be avoided (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Use in hepatic impairment.

Based on the experience with patients suffering from late stage primary biliary cirrhosis (PBC) with hepatic cirrhosis an increased systemic availability of budesonide in all patients with severely impaired hepatic function is to be expected. However, in patients with liver disease without hepatic cirrhosis in daily doses of 9 mg (3 x 3 mg) of budesonide was found to be safe and well tolerated. There are currently no data to support a specific dose recommendation for patients with non-cirrhotic liver diseases or only slightly impaired liver function is necessary.

Use in the elderly.

The experience in elderly with Budenofalk capsules is limited.

Paediatric use.

Budenofalk capsules are not recommended for use in children or adolescents. Long term effects, including on height and bone density have not been assessed.

Effects on laboratory tests.

As adrenal function may be suppressed by treatment with glucocorticoid, including budesonide, an ACTH stimulation test for diagnosing pituitary insufficiency might show false results (low values).

4.5 Interactions with Other Medicines and Other Forms of Interactions

Pharmacodynamic interactions.

Cardiac glycosides.

The action of the glycoside can be potentiated by potassium deficiency.

Saluretics.

Potassium excretion can be enhanced.

Pharmacokinetic interactions.

Cytochrome P450.

CYP3A4 inhibitors.

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 glucocorticoid side-effects, in which case patients should be monitored for systemic glucocorticoid side-effects. Ketoconazole 200 mg orally once daily increased the plasma concentrations of budesonide (3 mg single dose) approximately 6-fold during concomitant administration. When ketoconazole was administered 12 hours after budesonide, the concentrations increased approximately 3-fold. As there are not enough data to give dose recommendations, the combination should be avoided.
Other potent inhibitors of CYP3A4 such as ritonavir, itraconazole, clarithromycin, and grapefruit juice are also likely to cause a marked increase of the plasma concentrations of budesonide. Therefore concomitant intake of budesonide should be avoided.

CYP3A4 inducers.

Compounds or drugs such as carbamazepine and rifampicin, which induce CYP3A4, might reduce the systemic but also the local exposure of budesonide at the gut mucosa. An adjustment of the budesonide dose (using e.g. budesonide 3 mg capsules) might be necessary.

CYP3A4 substrates.

Compounds or drugs which are metabolized by CYP3A4 might be in competition with budesonide. This might lead to an increased budesonide plasma concentration if the competing substance has a stronger affinity to CYP3A4. Conversely, if budesonide has a stronger affinity to CYP3A4, the plasma concentrations of the competing substance might be increased and a dose-adjustment of this drug might be required.
Elevated plasma concentrations and enhanced effects of glucocorticoids have been reported in women also receiving oestrogens or oral contraceptives, but although this has not been observed with oral low dose combination contraceptives.
Cimetidine when administered at recommended doses in combination with budesonide has a small but insignificant effect on pharmacokinetics of budesonide. Omeprazole has no effect on the pharmacokinetics of budesonide.
Steroid-binding compounds. In theory, potential interactions with steroid-binding synthetic resins such as cholestyramine, and with antacids cannot be ruled out. If given at the same time as Budenofalk capsules, such interactions could result in a reduction in the effect of budesonide. Therefore, these preparations should be administered at least two hours apart.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

There are no data on the effect of budesonide on human fertility. Subcutaneous administration of budesonide to rats at doses up to 20 microgram/kg/day did not affect fertility.
(Category B3)
Administration during pregnancy should be avoided unless there are compelling reasons for therapy with Budenofalk capsules.
There are few data on pregnancy outcomes after oral administration of budesonide in humans. Although data on the use of inhaled budesonide in a large number of exposed pregnancies indicate no adverse effects, the maximal concentration of budesonide in plasma is expected to be higher with oral budesonide compared to inhaled budesonide.
In pregnant animals, administration of budesonide, like other glucocorticoids, has been shown to cause foetal death and abnormalities of foetal development (reductions in foetal/ pup growth and litter size, skeletal and visceral abnormalities). The relevance of these findings to humans has not been established.
 Budesonide is excreted in human milk. However, only minor effects on the breast-fed infant are anticipated after Budenofalk capsule intake within the therapeutic range. A decision should be made whether to discontinue breastfeeding or to discontinue Budenofalk capsules, taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.

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.

4.8 Adverse Effects (Undesirable Effects)

Budenofalk capsules are generally well tolerated. In clinical studies most adverse events were of mild to moderate intensity and of a nonserious character.
In two clinical trials involving 256 patients with acute Crohn's disease, budesonide was well tolerated. Table 1 shows the adverse events that occurred in at least 10% of patients in any of the two clinical trials included.

Post-marketing adverse effects.

The following undesirable effects and frequencies of Budenofalk capsules have been spontaneously reported.
The following frequency conventions are used in the evaluation 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) and very rare: (< 1/10,000), not known (cannot be estimated from the available data).
Common (≥ 1/100 to < 1/10). Depression, irritability, euphoria;
Muscle and joint pain, muscle weakness and twitching, osteoporosis;
Dyspepsia.
Uncommon (≥ 1/1,000 to < 1/100). Psychomotor hyperactivity, anxiety;
Duodenal or gastric ulcer.
Rare (≥ 1/10,000 to < 1/1,000). Aggression;
Glaucoma, cataract, blurred vision;
Pancreatitis;
Osteonecrosis;
Ecchymosis.
Very rare (< 1/10,000), including isolated reports.

Metabolism and nutritional disorders.

Oedema of legs, Cushing syndrome.

Nervous system disorders.

Pseudotumor cerebri (including papilloedema) in adolescents.

Gastrointestinal disorders.

Constipation.

General disorders.

Tiredness, malaise.
Some of the undesired effects were reported after long-term use.
Occasionally side effects may occur which are typical for systemic glucocorticoids. These side effects depend on the dosage, the period of treatment, concomitant or previous treatment with other glucocorticoids and the individual sensitivity.
Clinical studies showed that the frequency of glucocorticoid associated side effects is lower with Budenofalk capsules (approx. by half) than with oral treatment of equivalent dosages of oral prednisolone.

Systemically acting glucocorticoids.

Immune system disorders.

Interference with the immune response (e.g. increase in risk of infections).
An exacerbation or the reappearance of extraintestinal manifestations (especially affecting skin and joints) can occur on switching a patient from systemically acting glucocorticoids to the locally acting budesonide.

Metabolism and nutrition disorders.

Cushing syndrome: moon-face, truncal obesity, reduced glucose tolerance, diabetes mellitus, sodium retention with oedema formation, increased excretion of potassium, inactivity or atrophy of the adrenal cortex, growth retardation in children, disturbance of sex hormone secretion (e.g. amenorrhoea, hirsutism, impotence).

Psychiatric disorders.

Depression, irritability, euphoria.
In addition, a wide range of other psychiatric/ behavioural effects may occur.

Eyes disorders.

Glaucoma, cataract.

Vascular disorders.

Hypertension, increased risk of thrombosis, vasculitis (withdrawal syndrome after long-term therapy).

Gastrointestinal disorders.

Stomach complaints, gastroduodenal ulcer, pancreatitis.

Skin and subcutaneous tissue disorders.

Allergic exanthema, red striae, petechiae, ecchymosis, steroid acne, delayed wound healing, contact dermatitis.

Musculoskeletal, connective tissue and bone disorders.

Aseptic necrosis of bone (femur and head of the humerus).

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.

4.9 Overdose

Acute overdose with Budenofalk capsules is unlikely to result in clinical problems. 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.

The exact mechanism of action of budesonide in the treatment of Crohn's disease is not fully understood. The anti-inflammatory effects of budesonide, such as inhibition of the release of inflammatory mediators and suppression of the cellular immunological response, may be important. The intrinsic potency of budesonide, measured by its affinity to the glucocorticoid receptor, is about 15 times higher than the potency of prednisolone.
Data from clinical pharmacology studies and other controlled clinical trials strongly indicate that the mode of action of orally administered budesonide is predominantly based on a local action in the mucosa of the intestine and the colon due to its metabolism (by cytochrome P450 3A4) to pharmaceutically nearly inactive metabolites in the intestinal mucosa and in the liver. Doses of comparable clinical efficacy show that compared to prednisolone, Budenofalk capsules have a significantly lower influence on the hypothalamo-pituitary-adrenal (HPA) axis. At the recommended dosages, Budenofalk has significantly less effects on morning cortisol plasma levels, 24-hour cortisol plasma levels (AUC0-24) and 24-hour cortisol urine levels, than 20-40 mg prednisolone daily.

Clinical trials.

In a multicentre, randomised, controlled study (BUC-23/ CDA) the efficacy and safety of Budenofalk enteric capsules given at a dose of 3 mg TID was compared with a decreasing dose of prednisone (from 40 mg daily, reducing to 5 mg daily) over 8 weeks.
The Crohn's Disease Activity Index (CDAI) was the main clinical assessment for determining efficacy. The CDAI is a validated index based on subjective aspects rated by the patient (frequency of liquid or very soft stools, abdominal pain rating and general well-being) and objective observations (number of extra-intestinal symptoms, need for anti-diarrhoeal drugs, presence of abdominal mass, body weight and haematocrit).
The primary analysis was of a composite of selected steroid-related side effects and CDAI score.
Three types of responder were assessed. These were defined as:
"R1" responder - response without the occurrence of either "moon face" or "acne" (considered to be the main steroid-induced ADRs);
"R2" responder - response associated with the occurrence of at least one steroid-induced ADR;
"R0" responder - overall response (R1 or R2 response).
The overall response rate (R0) did not take differences in steroid side effects into consideration and included all patients with a CDAI < 150 at end of study and, in patients with a baseline CDAI < 210, a decrease in CDAI of ≥ 60. See Table 2.
In a double-blind, randomised, multicentre study (BUC-52/ CDA) the efficacy and safety of a 8 weeks treatment with Budenofalk capsules 9 mg/day (3 mg capsules three times daily or 3 x 3 mg capsules once daily) was compared to Salofalk tablets 4.5 g/day (3 x 500 mg tablets three times daily) in the therapy of active Crohn's disease.
The primary efficacy variable was clinical remission of Crohn's disease defined as CDAI score of ≤ 150 from baseline at the final visit (week 8) or at the withdrawal visit. Results showed that Budenofalk capsules are non-inferior to mesalazine in the treatment of active Crohn's disease (non-inferiority margin -10%). No significant difference in remission rate was observed for the 2 budesonide dosage regimens (budesonide 3 mg three times daily compared to budesonide 9 mg once daily). See Tables 3 and 4.
Results of the studies show that Budenofalk capsules are well tolerated in patients with active Crohn's disease (see Section 4.8 Adverse Effects (Undesirable Effects)).

5.2 Pharmacokinetic Properties

Absorption.

Budenofalk capsules are made from hard gelatin, which dissolves quickly in the stomach releasing the individual gastric juice-resistant granules, containing a total of 3 mg of budesonide in each capsule. There is a lag phase of 2 - 3 hours due to the delayed release of budesonide owing to the enteric coating on the granules.
In healthy volunteers, as well as in patients with Crohn's disease, mean maximal budesonide plasma concentrations of 1-2 nanogram/mL were seen about 5 hours following a single 3 mg oral dose of Budenofalk capsules, taken before a meal. The maximal release therefore occurs in the terminal ileum and caecum, the main area of inflammation in Crohn's disease.
In ileostomy patients, the release of budesonide from Budenofalk enteric capsules is comparable to healthy subjects or Crohn's disease patients.
Concomitant intake of food may delay release of granules from stomach by 2-3 hours, prolonging the lag phase to about 4-6 hours, without change in absorption rates.

Distribution.

Budesonide has a high volume of distribution (about 3 L/kg). Plasma protein binding averages 85-90%.

Biotransformation.

Budesonide undergoes extensive biotransformation in the intestinal mucosa and in the liver (approximately 90%) to metabolites of low glucocorticoid activity. The glucocorticoid activity of the major metabolites, 6β-hydroxybudesonide and 16α-hydroxyprednisolone, is less than 1% of that of budesonide.

Metabolism.

Budesonide is principally metabolised via cytochrome P450 (CYP) 3A4 in the intestinal mucosa and in the liver.

Excretion.

The average elimination half-life is about 3-4 hours. The systemic availability in healthy volunteers, as well as in fasting patients with Crohn's disease, is about 9-13%. The clearance rate is about 10-15 L/min for budesonide, determined by HPLC-based methods.

Specific patient populations (liver diseases).

Dependent on the type and severity of liver diseases and the fact that budesonide is metabolised by CYP3A4 in the liver, the metabolism of budesonide may be decreased in patients with liver diseases. Therefore, the systemic exposure of budesonide may be increased in patients with impaired hepatic function. With improving liver function and disease, metabolism of budesonide will normalize.
The bioavailability of budesonide (AUC) has been found to be significantly higher in patients with primary biliary cholangitis (PBC) who had liver cirrhosis (PBC Stage IV) compared to PBC patients without cirrhosis (PBC Stage I/II), following repeated daily administration of the daily dose of Budenofalk capsules (3 x 3 mg) once daily.

Budenofalk enteric capsules.

The mean peak plasma concentration of budesonide after a single Budenofalk 9 mg dose (3 x 3 mg capsules) was 1.73 ± 1.40 nanogram/mL at a median Tmax of 5.00 hours. For the metabolite 6-β-hydroxy-budesonide, the mean plasma concentration and Tmax were similar to budesonide (2.80 ± 1.26 nanogram/mL, and 5.5 hours, respectively). Higher concentrations were observed for the major metabolite 16-α-hydroxyprednisolone: the mean Cmax of 23.11 nanogram/mL occurred after a median Tmax of 5.45 hours. Of the 9 mg dose, 11.58% could be recovered in urine in form of 16-α-hydroxyprednisolone and 1.46% in form of 6-β-hydroxy-budesonide.
Pharmacokinetic data are summarised in Table 5 for the single 9 mg dose of Budenofalk capsules (3 x 3 mg budesonide) in 18 healthy subjects:
Pharmacokinetic data are summarised in Table 6 for Budenofalk 3 mg capsules (3 x 3 mg budesonide three times daily) in 12 healthy subjects:

5.3 Preclinical Safety Data

Genotoxicity.

Budesonide had no genotoxic effects in a battery of in vitro and in vivo tests.

Carcinogenicity.

The carcinogenic potential of budesonide has been assessed in mice and rats at respective oral doses up to 200 and 50 microgram/kg/day. No oncogenic effect was noted in mice. One study showed an increased incidence of malignant gliomas in male Sprague-Dawley rats given budesonide 50 microgram/kg/day. However this was not confirmed in further studies in male Sprague-Dawley and Fischer rats. 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. However this was also observed in rats treated with prednisolone and triamcinolone acetonide, thus indicating a class effect of glucocorticoids in rats.

6 Pharmaceutical Particulars

6.1 List of Excipients

Budenofalk capsules contain the following excipients: sugar spheres (sucrose), lactose monohydrate, povidone, methacrylic acid copolymer, ammonio methacrylate copolymer, triethyl citrate, purified talc, gelatin, erythrosine, sodium lauryl sulfate, titanium dioxide, iron oxide red and iron oxide black.

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 30°C.

6.5 Nature and Contents of Container

Budenofalk capsules are supplied in blister strips with aluminum foil backing.
Cartons of 9, 10, 50 and 90.*
*Not all pack sizes may be available.

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

Budesonide is a white or almost white, crystalline powder. It is practically insoluble in water, freely soluble in methylene chloride, sparingly soluble in alcohol.

Chemical structure.


Budesonide.

Proper name: Budesonide.
Chemical name: 16α,17α-butylidene dioxy-11β, 21-dihydroxy-1,4-pregnadiene-3, 20-dione.
C25H34O6 = 430.5.

CAS number.

51333-22-3.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

Summary Table of Changes