Consumer medicine information

Budenofalk Foam

Budesonide

BRAND INFORMATION

Brand name

Budenofalk Foam

Active ingredient

Budesonide

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Budenofalk Foam.

What is in this leaflet

This leaflet answers some common questions about BUDENOFALK foam. 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 using BUDENOFALK foam against the benefits they expect it will have for you.

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

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

What BUDENOFALK foam is used for

BUDENOFALK foam contains the active ingredient, budesonide. Budesonide belongs to a group of medications called corticosteroids. BUDENOFALK foam is used to treat ulcerative colitis (inflammation) of the rectum (back passage) and the lower part of the large bowel.

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

This medicine is not addictive.

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

BUDENOFALK foam is only available on a doctor’s prescription.

There is not enough information to recommend the use of this medicine for children or adolescents.

Before you use it

When you must not use it

Do not use BUDENOFALK foam if you have an allergy to:

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

Some symptoms of an allergic reaction may include shortness of breath, wheezing or difficulty breathing; swelling of the face, lips, tongue or other parts of the body; rash, itching or hives on the skin.

Do not use BUDENOFALK foam if you suffer from a severe liver disease (liver cirrhosis).

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

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

Before you start to use it

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

Tell your doctor if you are pregnant or plan to become pregnant or are breastfeeding or wish to breastfeed. Your doctor will discuss the risks and benefits of using BUDENOFALK foam if you are pregnant or breastfeeding.

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

  • 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
  • any other disease where use of corticosteroids may have unwanted effects.

If you have not told your doctor about any of the above, tell him/her before you start using BUDENOFALK foam.

Contact your doctor if you have been exposed to chicken pox, measles and shingles. They may become more severe when you use BUDENOFALK foam.

Tell your doctor if you have not yet had measles.

If you know that you need to be vaccinated please speak to your doctor first.

If you know that you are due to have an operation please tell your doctor that you are using BUDENOFALK foam.

If you have been treated with a stronger corticosteroid preparation before starting treatment with BUDENOFALK foam, your symptoms may reappear when the medicine is changed.

If this happens, contact your doctor.

Contact your doctor if you experience blurred vision or other visual disturbances.

Taking other medicines

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

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

  • 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 and rifampicin, medicines used to treat infections
  • ritonavir and cobicistat medicines used for treating HIV infections
  • carbamazepine, medicine used for treating epilepsy
  • rifampicin, medicine used to treat tuberculosis
  • contraceptive pill
  • cholestyramine, medicine used to reduce cholesterol level
  • cimetidine, medicine to reduce stomach acid.

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

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

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

How to use it

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 use

Adults and the elderly:
Each BUDENOFALK foam can contains enough budesonide for 14 applications, or 2 weeks of dosing, based on a standard dose of 2 mg/day.

Apply one actuation daily, corresponding to 2 mg budesonide. BUDENOFALK 2 mg foam can be applied in the morning or evening.

How to use it

If possible, go to the toilet and empty your bowels before using the foam.

  1. Wash your hands thoroughly with soap and water.
  2. Push the applicator firmly onto the spout of the spray can.

  1. Shake the can for 15 seconds to mix the contents.
  2. Each time you use a new can, remove the safety tab from under the pump dome.

  1. Twist the dome on top of the canister until the semi-circular gap underneath it is in line with the nozzle.

The spray can is now ready for use.
  1. Place your forefinger on top of the pump dome. Turn the spray can upside down. The pump dome must be pointing down.

  1. Stand with one foot on the floor and raise the other foot onto a chair or stool.
  2. Insert the applicator into the rectum as far as comfortable. To administer a dose of BUDENOFALK foam, push the pump dome fully once with your finger and hold for 5 seconds then very slowly lift your finger off the pump dome. The foam is being delivered at this time and you must wait 15 seconds for dosing to be complete.

  1. Withdraw the applicator from the rectum slowly.
  2. Remove the applicator from the spout of the spray can and dispose of it in the plastic bag provided as domestic waste.

  1. Wash your hands thoroughly and try not to empty your bowels again for as long as possible.

You may experience a little discomfort and a feeling of urgency to empty your bowels immediately after foam insertion. This is normal and expected due to the inflammation present within the bowel. Try to resist this urge to empty your bowels for as long as possible. This feeling will subside as treatment continues and the inflammation decreases.

When to use it

Use your medicine at about the same time each day. Using it at the same time each day will have the best effect. It will help you remember when to use it.

How long to use it

The duration of treatment will be decided by your doctor. In general, the acute episode subsides after 6 to 8 weeks. After this you should stop using BUDENOFALK foam.

BUDENOFALK foam helps control your condition but does not cure it. Therefore, you must continue to use BUDENOFALK foam for as long as your doctor tells you to.

If you forget to use it

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

Otherwise, use it as soon as you remember and then go back to taking your medicine as you would normally.

Do not use 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 use your medicine, ask your pharmacist for some hints.

If you use too much (overdose)

Immediately telephone your doctor or the Poisons Information Centre (telephone 13 11 26) for advice, or go to Accident and Emergency at the nearest hospital, if you think that you, or anyone else, may have used too much BUDENOFALK foam. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

While you are using it

Things you must do

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are using BUDENOFALK foam.

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

If you are going to have surgery, tell the surgeon or anaesthetist that you are taking BUDENOFALK foam. It may affect other medicines used during surgery.

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

Things that you must not do

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

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

Do not stop using your BUDENOFALK foam or change the dosage without checking with your doctor.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are using BUDENOFALK foam. Like all medicines, BUDENOFALK foam may have some 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.

Do not be alarmed by the following lists of side effects. You may not experience any of them.

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

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

  • signs or symptoms of an infection
  • headache
  • changes in behaviour such as depression, irritability, euphoria, restlessness, anxiety or aggression.

Common side effects (that affect less than 1 in 10 patients):

  • Burning or pain in the rectum
  • Cushing’s syndrome – e.g. with roundness of the face, weight gain, reduced glucose tolerance, high blood sugar, high blood pressure, fluid retention in the tissues (e.g. swollen legs), increased excretion of potassium (hypokalaemia), irregular periods in women, unwanted body hair in women, impotence, abnormal laboratory findings (reduced adrenal function), red stripes on the skin (stretch marks), acne.
  • indigestion, irritable stomach (dyspepsia)
  • increased risk of infection
  • muscle and joint pain, muscle weakness, muscle twitching
  • brittle bones (osteoporosis)
  • headache
  • mood changes, such as depression, irritability or euphoria
  • rash from hypersensitivity reactions, red spots from bleeding in the skin, delayed wound healing, local skin reactions such as contact dermatitis.

Uncommon side effects (that affect less than 1 in 100 patients):

  • changes to the blood (increase in erythrocyte sedimentation rate, increase in the number of white blood cells)
  • ulcers in the stomach or small intestine
  • giddiness, disturbance of smell
  • urinary tract infections
  • sleeplessness, restlessness with increased physical activity, anxiety
  • nausea, abdominal pain, dyspepsia, wind, tingling in the abdomen, anal fissure, mouth rash, urgent need to empty the bowels,rectal bleeding
  • changes in liver function
  • changes in pancreatic function, changes in adrenal hormones
  • acne, increased sweating
  • increase in appetite.

Rare side effects (may affect up to 1 in 1,000 people):

  • blurred vision
  • inflammation of the pancreas
  • bone loss due to poor circulation of blood (osteonecrosis)
  • aggression
  • bruising.

Very rare side effects (may affect up to 1 in 10,000 people):

  • slowed growth in children
  • constipation
  • increased pressure in the brain, possibly with increased pressure in the eye (swelling of the optic disk) in adolescents
  • increased risk of blood clotting, inflammation of the blood vessels (associated with stopping corticosteroid use after long-term therapy)
  • tiredness, general feeling of being ill.

These side effects are typical of corticosteroid medications and most of them can also be expected for treatments with other corticosteroids. They may occur depending on your dose, duration of treatment, whether you have had or are having treatment with other corticosteroid preparations, and your individual susceptibility.

Some of these unwanted effects were only reported after long-term use of oral budesonide.

In general, the risk of side effects with BUDENOFALK foam is lower than with systemically acting (affecting the whole body) corticosteroid preparations due to its local action.

If you have been treated with a stronger corticosteroid preparation before starting treatment with BUDENOFALK foam, your symptoms may reappear when the medicine is changed.

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

After using it

Storage

Keep BUDENOFALK foam in its original packaging until it is time to use it.

Keep BUDENOFALK foam in a cool dry place where the temperature stays below 25°C.

Do not refrigerate or freeze. Protect from direct sunlight.

Keep away from flames or sparks. Contains flammable gas.

Use within 4 weeks of first opening.

Do not store BUDENOFALK foam 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 using BUDENOFALK foam or the expiry date has passed, ask your pharmacist what to do with any foam that is left over.

Do not pierce or burn the can even when empty.

Ingredients

Each dose/actuation of BUDENOFALK foam contains 2 mg of the active ingredient, budesonide.

Each container of BUDENOFALK foam also contains cetyl alcohol, emulsifying wax, purified water, disodium edetate, steareth-10, propylene glycol, citric acid monohydrate and butane, isobutane and propane as propellants.

Available in the following packs:

  • One pressurised container with 14 applicators and 14 plastic bags
  • Two pressurised containers, with 28 applicators and 28 plastic bags.

Not all pack sizes are currently available in Australia.

Plastic bags are for the hygienic disposal of the applicators.

Sponsor

Dr Falk Pharma Australia Pty Ltd, 815 Pacific Highway, Chatswood, NSW 2067

Australian Registration Number:
AUST R 179575

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

This leaflet was revised in November 2020

Published by MIMS February 2021

BRAND INFORMATION

Brand name

Budenofalk Foam

Active ingredient

Budesonide

Schedule

S4

 

1 Name of Medicine

Budesonide.

2 Qualitative and Quantitative Composition

Budenofalk foam contains the active ingredient budesonide.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Foam.

4 Clinical Particulars

4.1 Therapeutic Indications

Budenofalk foam is indicated in the treatment of active rectal and rectosigmoid disease in ulcerative colitis.

4.2 Dose and Method of Administration

For adults aged > 18 years of age.

Apply one actuation of 2 mg budesonide daily. Budenofalk 2 mg foam can be applied in the morning or evening.
Budenofalk 2 mg foam should be in room temperature when applied.
The canister is first fitted with an applicator and then shaken for about 15 seconds before the applicator is inserted into the rectum as far as comfortable. Note that the dose is only sufficiently accurate when the pump dome is held downwards as vertically as possible. To administer a dose of Budenofalk 2 mg foam, the pump dome is fully pushed down and very slowly released. Following the activation the applicator should be held in position for 10-15 seconds before being withdrawn from the rectum.
The best results are obtained when the intestine is evacuated prior to administration of Budenofalk 2 mg foam.
The attending physician determines the duration of use. An acute episode generally subsides after 6 to 8 weeks.
Treatment may be continued in patients showing progressive improvement, but it should not be persisted with if the response has been inadequate. Continuous treatment beyond 8 weeks has not been assessed. Budenofalk 2 mg foam should not be used after this time.
Topical steroids including Budenofalk have not been shown to be effective in the maintenance of remission of ulcerative colitis.
Do not use Budenofalk foam after 4 weeks of first opening the container.

4.3 Contraindications

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

4.4 Special Warnings and Precautions for Use

Identified precautions.

Topical steroids have not been demonstrated to maintain remission in ulcerative colitis. Budenofalk should only be used for treatment of active ulcerative colitis. Treatment should not continue beyond 8 weeks.
Treatment with Budenofalk foam results in lower systemic steroid levels than conventional oral steroid therapy. Particular care is needed in patients who are transferred from systemic glucocorticosteroid treatment with higher systemic effect to Budenofalk foam. 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.
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 corticosteroids may occur, particularly when prescribed at high doses and for prolonged periods. Such effects may include Cushing's 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)).
Corticosteroids 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 glucocorticosteroids, 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 nonimmune patients who are receiving systemic corticosteroids or who have used them within the previous 3 months; this should be given within 10 days of exposure to chickenpox. If a diagnosis of chickenpox is confirmed, the illness warrants specialist care and urgent treatment. Corticosteroids should not be stopped and the dose may need to be increased.

Measles.

Patients 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 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.
Concomitant treatment with ketoconazole or other CYP3A4 inhibitors should be avoided (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
This medicine contains cetyl alcohol and propylene glycol, which can cause local skin reactions (e.g. contact dermatitis).

Use in hepatic impairment.

Based on the experience with oral preparations of budesonide in 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 oral budesonide in daily doses of 3 mg TID was safe and well tolerated. There is no evidence that a specific dose recommendation for patients with noncirrhotic liver diseases or only slightly impaired liver function is necessary. As the plasma levels of budesonide appear to be generally slightly higher with rectal budesonide, Budenofalk foam should be used only with caution in patients with hepatic impairment.

Use in the elderly.

The experience in elderly with Budenofalk foam is limited.

Paediatric use.

Budenofalk foam is 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.

Because adrenal function may be suppressed by treatment with 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 corticosteroid side-effects, in which case patients should be monitored for systemic corticosteroid 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 application 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 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, or, if budesonide binds stronger to CYP3A4, the competing substance might be increased in plasma and a dose adaption/ reduction of this drug might be required.
Elevated plasma concentrations and enhanced effects of corticosteroids have been reported in women also receiving oestrogens or oral contraceptives, but this has not been observed with oral low dose combination contraceptives.

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 foam.
There are no data on pregnancy outcomes after rectal 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 rectal budesonide compared to inhaled budesonide.
In pregnant animals, administration of budesonide, like other glucocorticoids, has been shown to cause fetal death and abnormalities of fetal development (reductions in fetal/ 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 breastfed infant are anticipated after Budenofalk administration within the therapeutic range. A decision should be made whether to discontinue breastfeeding or to discontinue Budenofalk 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)

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.
In clinical trial BUF-6/UCA involving a total of 120 patients receiving Budenofalk foam budesonide was well tolerated. Table 1 shows the adverse events:
Undesirable effects were reported in 14% of patients in clinical trials with Budenofalk foam. Burning in the rectum or pain were common, and nausea, headache and an increase in liver enzymes were uncommon.

Post-marketing adverse effects.

The following suspect adverse drug reactions presented by body system have been spontaneously reported in international postmarketing surveillance as well as in clinical trials of Budenofalk preparations including enteric capsules and foam.
The assessment of undesirable effects is based on the following frequencies: 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), including isolated reports.

Adverse drug reactions by frequency and system organ class (SOC).

Infections and parasitic diseases.

Uncommon: urinary tract infections.

Blood and lymphatic system disorders.

Uncommon: anaemia, increase in erythrocyte sedimentation rate, leukocytosis.

Metabolism and nutrition disorders.

Uncommon: increased appetite.

Psychiatric disorders.

Common: Depression, irritability, euphoria.
Uncommon: insomnia, psychomotor hyperactivity, anxiety.
Rare: aggression.

Musculoskeletal and connective tissue disorders.

Common: Muscle and joint pain, muscle weakness and twitching, osteoporosis.
Rare: Osteonecrosis.

Eye disorders.

Rare: Glaucoma, cataract, blurred vision.

Nervous system disorders.

Uncommon: headache, dizziness, disturbances of smell.

Vascular disorders.

Uncommon: hypertension.

Gastrointestinal disorders.

Common: dyspepsia.
Uncommon: nausea, abdominal pain, flatulence, abdominal complaints, anal fissure, aphthous stomatitis, frequent urge to defecate, haemorrhoids, rectal bleeding, duodenal and gastric ulcer.
Rare: pancreatitis.

Hepatobiliary disorders.

Uncommon: increase in transaminases (ALT, AST), increase in parameters of cholestasis (GGT, AP).

Skin and subcutaneous tissue disorders.

Uncommon: acne, increased sweating.
Rare: ecchymosis.

Investigations.

Uncommon: increase in amylase, change in cortisol.

General disorders and administration site conditions.

Common: burning in the rectum and pain.
Uncommon: asthenia, increase in body weight.

Systemically acting glucocorticoids.

Occasionally side effects may occur which are typical for systemically acting glucocorticoids. These side effects, listed below, depend on the dosage, the period of treatment, concomitant or previous treatment with other glucocorticoids and the individual sensitivity.

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 the systemically acting glucocorticosteroids to the locally acting budesonide.

Metabolism and nutrition disorders.

Cushing's 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.

Eye disorders.

Glaucoma, cataract.

Nervous system disorders.

Pseudotumor cerebri (including papilloedema) in adolescents.

Vascular disorders.

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

Gastrointestinal disorders.

Stomach complaints, duodenal ulcer, pancreatitis, constipation.

Skin and subcutaneous tissue disorders.

Allergic exanthema, red striae, petechiae, ecchymoses, steroid acne, delayed wound healing. Local skin reactions such as contact dermatitis may occur.

Musculoskeletal, connective tissue and bone disorders.

Aseptic bone necrosis (femur and head of the humerus), diffuse muscle pain and weakness, osteoporosis.

General disorders.

Tiredness, malaise.
Some of these undesired effects were reported after long-term use of orally administered budesonide.
There are no data on the long term use of Budenofalk foam in patients with ulcerative colitis and long term use is not recommended.
Due to its local action, the risk of undesired effects of Budenofalk foam is generally lower than with systemically acting glucocorticoids.

4.9 Overdose

To date, no cases of overdosage with budesonide are known. In view of the properties of budesonide contained in Budenofalk 2 mg foam, an overdose resulting in toxic damage is extremely unlikely. 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.

Pharmacodynamic properties.

The exact mechanism of action of budesonide in the treatment of ulcerative colitis/ procto-sigmoiditis is not fully understood. Data from clinical pharmacology studies and controlled clinical trials strongly indicate that the mode of action of budesonide is predominantly based on a local action in the gut. Budesonide is a glucocorticoid with a high local anti-inflammatory effect. At a dosage of 2 mg budesonide, applied rectally, budesonide leads to practically no suppression of the hypothalamus-hypophysis-adrenal cortex axis.
Budenofalk 2 mg foam investigated up to the daily dosage of 4 mg budesonide showed virtually no influence on the basal plasma cortisol level.

Clinical trials.

Study BUF-6/UCA was an active controlled, multicentre, randomised, open label, parallel group trial involving 251 patients with proctitis or proctosigmoiditis. A rectally applied hydrocortisone comparator (hydrocortisone acetate 100 mg foam [Colifoam]) was compared to budesonide 2 mg (Budenofalk) foam.
This study was designed to demonstrate equivalence between the two treatments with equivalence to be confirmed if the 95% CI for the between group difference in remission rate was no more than 15%. Equivalence was demonstrated only in the intent to treat population, not in the per protocol population.
The primary efficacy parameter for this study was clinical remission defined as Disease Activity Index (DAI) ≤ 3 at the end of the 8 week treatment. DAI is defined as the sum of the scores of four parameters: weekly stool frequency, weekly rectal bleeding, mucosal appearance and physician's rating of disease activity (see Table 2).

5.2 Pharmacokinetic Properties

Absorption.

After oral administration, the systemic availability of budesonide is about 10%. After rectal administration the AUC is about 1.5-fold higher than in historical controls considering the identical oral budesonide dose. Peak levels are obtained after an average of 2-3 hours after administering Budenofalk 2 mg foam.

Distribution.

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

Metabolism.

Budesonide undergoes extensive biotransformation 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.

Excretion.

The average elimination half-life is about 3-4 hours. The mean clearance rate is about 10-15 L/min for budesonide, determined by HPLC based methods.

Specific patient populations (liver disease).

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

Budenofalk foam.

The systemic bioavailability was calculated to be 15.3% and 13.8% after single and multiple dosing, respectively. Comparison of data after single and multiple dosing reveals no indication for a potential accumulation of budesonide in serum.
Pharmacokinetic data are summarised in Table 3 for Budenofalk 2 mg foam after single dose and steady state dosing in 18 healthy subjects:
Scintigraphic study of a single rectal dose of 99mTc labelled budesonide 2 mg (Budenofalk) foam in 12 patients showed that the spread of the budesonide foam ranged between 11 and 40 cm (mean of 25.4 ± 10.3 cm) depending on the individual patient (this range includes from reaching the distal half of the sigmoid, to reaching the proximal third of the descending colon). The maximal spread was reached between 2 and 6 hours (mean of 4 hours) depending on the individual patient and remained relatively stable between 4 hours and 6 hours. The distal half sigmoid was reached in all patients on average after 2 hours and accounted for 27.4% of the radiolabelled budesonide foam at 2 hours.
This study maximised conditions for spread of budesonide within the colon by having study subjects undergo a prestudy colonoscopy which would have emptied the bowel of faecal matter and by having them lie down for 4 hours after administration. It is anticipated that in clinical practice the spread would be somewhat less than was demonstrated in this study.

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 corticosteroids in rats.

6 Pharmaceutical Particulars

6.1 List of Excipients

Budenofalk foam contains the following excipients: cetyl alcohol, emulsifying wax, purified water, disodium edetate, steareth-10, propylene glycol, citric acid monohydrate and butane, isobutane and propane as propellants.

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. Do not refrigerate or freeze.
This is a pressurised container, containing flammable propellant.
Do not expose to temperature higher than 50°C, protect from direct sunlight.
Do not pierce or burn even when empty.

6.5 Nature and Contents of Container

Budenofalk foam is supplied in aluminium pressurised container with metering valve together with 14 PVC applicators coated with white soft paraffin and liquid paraffin for administration of the foam and 14 plastic bags for hygienic disposal of the applicators.
Pack sizes: Original pack with 1 pressurised container, contains at least 14 doses of 1.2 g foam each.*
Original pack with 2 pressurised containers, contain at least 2 x 14 doses of 1.2 g foam each.
(*Currently not marketed.)

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

Chemical structure.


Chemical name: 16α,17α-butylidene dioxy-11β, 21-dihydroxy-1,4-pregnadiene-3, 20-dione C25H34O6 = 430.5.
Budesonide is a white or almost white, crystalline powder. It is practically insoluble in water, freely soluble in methylene chloride, sparingly soluble in alcohol.

CAS number.

51333-22-3.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

Summary Table of Changes