Consumer medicine information

Jorveza

Budesonide

BRAND INFORMATION

Brand name

Jorveza

Active ingredient

Budesonide

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Jorveza.

SUMMARY CMI

Jorveza®

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 JORVEZA?

JORVEZA tablets contain the active ingredient, budesonide. JORVEZA tablets are used in adult patients to treat eosinophilic oesophagitis (EoE) which is an inflammatory condition of the gullet (food pipe) that causes problems with swallowing food.

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

2. What should I know before I take JORVEZA?

Do not take if you have ever had an allergic reaction to JORVEZA tablets 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 JORVEZA? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with JORVEZA tablets 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 JORVEZA?

  • Adults: The recommended dose for treatment of acute episodes is two 1 mg tablets per day. Take one 1 mg tablet in the morning and one in the evening.
  • The recommended dose for prevention of further episodes is two 0.5 mg tablets (1 mg budesonide) per day or two 1 mg tablets (2 mg budesonide) per day, depending on your response to the treatment. Take one tablet in the morning and one tablet in the evening. Your doctor will decide which dose is best for you.

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

5. What should I know while taking JORVEZA?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are using JORVEZA tablets.
  • If you become pregnant while using this medicine, tell your doctor immediately.
Things you should not do
  • Do not take JORVEZA tablets 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 using JORVEZA 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 JORVEZA in their original packaging until it is time to take them.
  • Keep your tablets in a cool dry place where the temperature stays below 25°C. Protect from light and moisture.
  • 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 JORVEZA? 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 of taking JORVEZA are: fungal infections in the gullet (food pipe), mouth and throat, headache, feeling sick (nausea), heartburn, indigestion, tingling or numbness in your mouth, dry mouth, taste disorder, burning tongue, upper abdominal (belly) pain, tiredness, decreased amount of the hormone cortisol in your blood, dry eyes, difficulty in sleeping, problems with tongue and cold sore (oral herpes).

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

Jorveza®

Active ingredient: Budesonide 0.5 mg and 1 mg orally disintegrating tablets

Consumer Medicine Information (CMI)

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

Where to find information in this leaflet:

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

1. Why am I taking JORVEZA?

JORVEZA tablets contain the active ingredient, budesonide. Budesonide belongs to a group of medications called corticosteroids.

JORVEZA tablets are used to treat eosinophilic oesophagitis (EoE) which is an inflammatory condition of the gullet (food pipe) that causes problems with swallowing food.

2. What should I know before I take JORVEZA?

Warnings

Do not take JORVEZA 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 take this medicine.
  • Do not take this medicine if you have uncontrolled infections or active tuberculosis.
  • 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 especially the following:
    - liver disease or kidney disease
    - lung disease (e.g. 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 (cloudy area in your eye)
    - family history of diabetes or glaucoma
    - any infection
    - recent or planned surgery
    - other stresses
    - any other disease where use of corticosteroids may have unwanted effects
  • are on other corticosteroid treatments.
  • get fungal infections in the mouth, throat (symptoms can be white spots) or in the gullet or if you think you have any infection during treatment with JORVEZA. The symptoms of some infections can be unusual or less pronounced when taking JORVEZA.
  • have been exposed to chicken pox, measles and shingles infections. These illnesses may become more severe when you take JORVEZA.
  • have not yet had measles.
  • know that you need to be vaccinated, please speak to your doctor first.
  • know that you are due to have an operation, please tell your doctor that you are taking JORVEZA.
  • have been treated with a stronger corticosteroid preparation before starting treatment with JORVEZA, your symptoms may reappear when the medicine is changed. If this happens, contact your doctor.
  • experience blurred vision or other visual disturbances.

Keep away from people who have chicken pox, measles or herpes zoster (shingles), if you have never had them.

If you develop swelling of your face, particularly around your mouth (lips, tongue or throat) and/or difficulties to breathe or swallow, stop taking JORVEZA and seek urgent medical attention. These may be signs of an allergic reaction, which may also include rash and itching.

JORVEZA 0.5 mg and 1 mg contains 26 mg of sodium (the main component of cooking/table salt) in each tablet. Therefore, the maximum daily dose of sodium from either strength when taken as advised (2 x 1 mg or 2 x 0.5 mg tablets) is 52 mg per day. This is equivalent to approximately 2.6% of the recommended maximum daily dietary intake of sodium for an adult.

JORVEZA could affect the results of adrenal function tests (ACTH stimulation test) ordered by your doctor or in hospital. Tell your doctors that you are taking JORVEZA before you have any tests.

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 JORVEZA 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 JORVEZA 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 and erythromycin (medicines used to treat infections)
  • ritonavir and cobicistat (medicines used to treat HIV infections)
  • oestrogens (contraceptive pill)

These medicines may be affected by JORVEZA or they may affect how well JORVEZA works. 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. Grapefruit juice contains some components that influence the metabolism (breakdown) of JORVEZA. This can worsen its side effects.

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

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

4. How do I take JORVEZA tablets?

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

How much to take

  • The recommended dose for treatment of acute episodes is two 1 mg tablets per day. Take one 1 mg tablet in the morning and one in the evening.
  • The recommended dose for prevention of further episodes is two 0.5 mg tablets (1 mg budesonide) per day or two 1 mg tablets (2 mg budesonide) per day, depending on your response to the treatment. Take one tablet in the morning and one tablet in the evening. Your doctor will decide which dose is best for you.

Speak to your doctor if you want to interrupt or end your JORVEZA treatment early. It is important that you do not stop taking JORVEZA without talking to your doctor.

Keep taking JORVEZA until your doctor tells you to stop, even if you feel better.

When to take JORVEZA

Take your medicine twice a day (once in the morning and once at night) after 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 JORVEZA

  • Take the JORVEZA tablet immediately once removed from the blister package.
  • Take JORVEZA after a meal.
  • Place the tablet on the tip of your tongue and close your mouth. Press it gently against the roof of your mouth with your tongue until it has disintegrated completely (this takes between 2 and 5 minutes on average but may take up to 10 minutes or longer in some patients). Saliva will be produced while the JORVEZA tablet is disintegrating. Swallow the disintegrated material slowly, as the tablet breaks up.
  • Do NOT take any liquid or food with the tablet.
  • Do not chew or swallow the tablet if not disintegrated.
  • Do not eat, drink, brush your teeth or rinse your mouth for at least 30 minutes after you have taken the tablet. Do not use any oral solutions, sprays or chewable tablets for at least 30 minutes before or after administration of the tablet. This will ensure that your medicine works properly.

The following QR code links to a patient instructions for use video, which covers the same dosing procedure detailed above:

How long to take JORVEZA

Initially, your treatment should last about 6 to 12 weeks. After this initial treatment, your doctor will decide for how long and which dose (1 mg/day or 2 mg/day) you should continue to take, depending on your condition and your response to the treatment.

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

If you forget to take JORVEZA

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. This may increase the chance of 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 JORVEZA

If you think that you have taken too much JORVEZA no emergency medical treatment is required. If you have any concerns, you should:

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

5. What should I know while taking JORVEZA?

Things you should do

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

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

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

It may affect other medicines used during surgery.

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

Things you should not do

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

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

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

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 JORVEZA in the original packaging until it is time to take them. If you take out of the packaging before you plan to dose, they may not keep well.
  • Store below 25°C.

Follow the instructions on the carton on how to take care of your medicine properly.

Store JORVEZA in a cool dry place away from moisture, heat or sunlight, for example, do not store it:

  • in the bathroom or near a sink; or
  • in the car or on window sills.

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 taking JORVEZA:
Very common side effects include:
  • fungal infections in the gullet (which can cause pain or discomfort when swallowing)
  • fungal infections in the mouth and throat (possible signs include white spots in the mouth or throat)
Common side effects include:
  • headache
  • feeling sick (nausea)
  • heartburn
  • indigestion
  • tingling or numbness in your mouth, dry mouth
  • taste disorder, burning tongue
  • upper abdominal (belly) pain
  • tiredness
  • decreased amount of the hormone cortisol in your blood
  • dry eyes
  • difficulty in sleeping
  • problems with tongue
  • cold sore (oral herpes).
Uncommon side effects include:
  • high blood pressure
  • anxiety, agitation
  • dizziness
  • cough, dry throat, sore throat, common cold
  • abdominal (belly) pain, abdominal distension (bloating)
  • difficulty swallowing
  • inflammation of the stomach, ulcers in the stomach
  • swelling of the lips
  • rash, itching rash
  • sensation of foreign body
  • pain in the mouth or throat
  • painful gums
  • decreased level of osteocalcin, weight gain.
Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
Symptoms of allergic reaction:
  • swelling of the face, particularly of the eyelids, lips, tongue or throat (angioedema)
  • shortness of breath
  • itchy rash or hives.
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 JORVEZA tablets (corticosteroids). These side effects are typical for systemically acting preparations. As JORVEZA tablets act locally, the risk of these class effects occurring with this medicine are generally expected to be lower than with systemically acting corticosteroids.

Possible class effects of systemically acting corticosteroids are:

  • Cushing Syndrome: roundness of the face, weight gain, acne, increased risk of high blood sugar, fluid retention (e.g. swollen legs)
  • slowed growth in children
  • increased risk of infection
  • irregular periods in women, male hair growth patterns in women
  • impotence
  • mood changes such as depression, irritation or euphoria
  • restlessness with increased physical activity and aggression
  • blurred vision (e.g. glaucoma and cataract)
  • increased risk of blood clotting, disease of the blood vessels (associated with stopping corticosteroid use after long term therapy)
  • ulcers in the small intestine, pancreatitis and constipation
  • muscle and joint pain, muscle weakness, muscle twitching
  • bone weakness (osteoporosis), bone damage due to poor circulation of blood (osteonecrosis)
  • rash from hypersensitivity reactions (allergic exanthema), formation of red stripes (striations) and bleeding in the skin, delayed wound healing, bruising
  • general feeling of being ill
  • increased brain pressure with possible additional swelling of the optic disk in adolescents.

These side effects are typical for systemic corticosteroids, such as prednisolone. Due to the local action of JORVEZA tablets, the risk of systemic adverse reactions is generally lower than when taking systemically acting corticosteroids.

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 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 JORVEZA tablets contains

Active ingredient
(main ingredient)		Budesonide 1 mg or 0.5 mg
Other ingredients
(inactive ingredients)		magnesium stearate
sodium acid citrate
sodium dihydrogen citrate
docusate sodium
sucralose
sodium bicarbonate
mannitol
macrogol 6000
povidone
Potential allergensucralose

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

What JORVEZA tablets looks like

JORVEZA 1 mg orally disintegrating tablets: white or almost white, round tablets with a smooth surface and facet.

They are available in blisters of 20, 30, 60 and 90 tablets*.

* Not all pack sizes may be marketed

JORVEZA 0.5 mg orally disintegrating tablets: white, round tablets debossed with “0.5” on one side and smooth on the other side.

They are available in blisters of 20, 60, 100 and 200 tablets*.

* Not all pack sizes may be marketed.

Australian Registration Number:

JORVEZA 1 mg orally disintegrating tablets:

AUST R 322645

JORVEZA 0.5 mg orally disintegrating tablets:

AUST R 350996

Who distributes JORVEZA tablets

JORVEZA® is supplied in Australia by:

Dr Falk Pharma Australia Pty Ltd
9 Help Street
Chatswood, NSW 2067
Australia
Phone: 1800 DRFALK (373 255)

JORVEZA® is supplied in New Zealand by:

Dr Falk Pharma New Zealand Ltd
29 Northcroft Street
Takapuna, Auckland 0622
New Zealand
Phone: 0800 44 88 69

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

This leaflet was prepared in October 2024.

Published by MIMS March 2025

BRAND INFORMATION

Brand name

Jorveza

Active ingredient

Budesonide

Schedule

S4

 

1 Name of Medicine

Budesonide.

2 Qualitative and Quantitative Composition

Each orally disintegrating tablet contains either 0.5 mg or 1 mg of budesonide.
Each budesonide orally disintegrating tablet also contains sucralose and sodium.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Orally disintegrating tablet.

Jorveza 0.5 mg tablet.

White or almost white, round, biplane orally disintegrating tablet with '0.5' debossed on one side.

Jorveza 1 mg tablet.

White or almost white, round, biplane orally disintegrating tablet.

4 Clinical Particulars

4.1 Therapeutic Indications

Jorveza is indicated for the treatment of eosinophilic oesophagitis (EoE) in adults.

4.2 Dose and Method of Administration

The treatment with this medicinal product should be initiated by a physician experienced in the diagnosis and treatment of eosinophilic oesophagitis.

Dosage.

The recommended daily dose for induction treatment is 2 mg budesonide as one 1 mg tablet in the morning and one 1 mg tablet in the evening.
The usual duration of induction treatment is 6 weeks. For patients who are not appropriately responding during 6 weeks the treatment can be extended to up to 12 weeks.
If a dose is missed, treatment should be continued at the prescribed dosage. A double dose should not be used to make up for a forgotten dose.
The recommended daily dose for maintenance of remission is 1 mg budesonide as one 0.5 mg tablet in the morning and one 0.5 mg tablet in the evening, or 2 mg budesonide as one 1 mg tablet in the morning and one 1 mg tablet in the evening, depending on the individual clinical requirement of the patient.
The maintenance dose of 1 mg budesonide twice daily is recommended for patients with a long-standing disease history and/or high extent of oesophageal inflammation in their acute disease state, also see Section 5.1 Pharmacodynamic Properties.
The duration of maintenance therapy is determined by the treating physician.

Method of administration.

Jorveza should be taken after a meal.
It should be placed on the tip of the tongue and gently pressed against the top of the mouth, where it will disintegrate. This will usually take between two and five minutes, but can take up to 10 minutes or longer in some patients. The effervescence process starts after the orally disintegrating tablet comes into contact with saliva and stimulates the production of further saliva in which the released budesonide mixes and which the patient is instructed to swallow slowly. This enables the surface of the oesophagus to be exposed to comparatively high concentrations of budesonide over a relatively long period of time from this budesonide-loaded saliva. Therefore, the saliva, with its mucoadhesive properties, acts like a biologic vehicle, facilitating optimal targeting of the budesonide from the orally disintegrating tablet at the site of the inflammation in the oesophagus of patients with EoE.
Jorveza should not be taken with liquid or food.
There should be at least 30 minutes after dosing before eating or drinking or performing oral hygiene. Any oral solutions, sprays or chewable tablets should also not be used for at least 30 minutes before or after administration of Jorveza.
Jorveza should not be chewed or swallowed if not disintegrated.
The above measures ensure optimal exposure of the oesophageal mucosa to budesonide.
Jorveza should be taken immediately once removed from the blister package.

Special populations.

Renal impairment.

There are currently no data available for patients with renal impairment. Because budesonide is not excreted via the kidneys, patients with mild to moderate impairment may be treated with caution with the same doses as patients without renal impairment. Budesonide is not recommended for use in patients with severe renal impairment.

Hepatic impairment.

During treatment of patients with hepatic impairment with other budesonide containing medicinal products, budesonide levels were increased. However, no systematic study investigating the impact of different degrees of hepatic impairment on the bioavailability of budesonide has been conducted. In the absence of these data, patients with hepatic impairment should not be treated with Jorveza (see Section 4.4 Special Warnings and Precautions for Use; Section 5.2 Pharmacokinetic Properties).

Paediatric population.

The safety and efficacy of Jorveza in children and adolescents under the age of 18 years have not been established. No data are available; (see Section 4.4 Special Warnings and Precautions for Use).

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed, see Section 6.1.
Jorveza is contraindicated in patients with uncontrolled infections or active tuberculosis.

4.4 Special Warnings and Precautions for Use

Infections.

Suppression of the inflammatory response and immune function increases the susceptibility to infections and their severity. Symptoms of infections can be atypical or masked.
In clinical studies conducted with Jorveza, oral, oropharyngeal and oesophageal candida infections have been observed at high frequency (see Section 4.8 Adverse Effects (Undesirable Effects)).
If indicated, symptomatic candidiasis of the mouth and throat can be treated with orally active antifungal therapy whilst still continuing treatment with Jorveza.
Chickenpox, herpes zoster and measles can have a more serious course in patients treated with glucocorticoids. In patients who have not had these diseases, the vaccination status should be checked, and particular care should be taken to avoid exposure. If patients are infected or suspected of being infected, consider reduction or discontinuation of glucocorticoid treatment.

Vaccines.

The co-administration of live vaccines and glucocorticoids should be avoided as this is likely to reduce the immune response to vaccines. The antibody response to other vaccines may be diminished.

Special populations.

Patients with tuberculosis, hypertension, diabetes mellitus, osteoporosis, peptic ulcer, glaucoma, cataract, family history of diabetes or family history of glaucoma may be at higher risk of experiencing systemic glucocorticoid adverse reactions, especially from systemically acting glucocorticoids (see below and see Section 4.8 Adverse Effects (Undesirable Effects)) and should therefore be monitored for the occurrence of such effects. In these patients, caution should be exercised and the benefits of a topical glucocorticoid, such as Jorveza, must be weighed against its risk. Jorveza should not be used in patients with active tuberculosis or uncontrolled infection.

Use in hepatic impairment.

Reduced liver function may affect the elimination of budesonide, causing higher systemic exposure. The risk of adverse reactions (systemic glucocorticoid effects) will be increased. However, no systematic data are available. In the absence of these data, patients with hepatic impairment should therefore not be treated with Jorveza.

Renal impairment.

There are currently no data available for patients with renal impairment. Because budesonide is not excreted via the kidneys, patients with mild to moderate impairment may be treated with caution with the same doses as patients without renal impairment. In the absence of specific data, Jorveza is not recommended for use in patients with severe renal impairment.

Use in the elderly.

There are insufficient data concerning the use of Jorveza in patients aged ≥ 65 years. Caution should be exercised in elderly patients due to the potential for decreased hepatic, renal or cardiac function, or due to other intercurrent conditions or diseases as well as the administration of specific concomitant therapies (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Paediatric use.

The safety and efficacy of Jorveza in children and adolescents under the age of 18 years have not been established; no data are available. Jorveza should not be used in children and adolescents under the age of 18 years. Glucocorticoids, including Jorveza, may reduce growth velocity in children.

Systemic effects of glucocorticoids.

Systemic effects of glucocorticoids (e.g. Cushing's syndrome, adrenal suppression, growth retardation, cataract, glaucoma, decreased bone mineral density and a wide range of psychiatric effects) may occur (also see Section 4.8 Adverse Effects (Undesirable Effects), particularly when prescribed at high doses and for prolonged periods, especially with systemically acting glucocorticoids. These adverse reactions also depend on concomitant and previous glucocorticoid treatment, the individual sensitivity and the glucocorticoid levels achieved in the systemic circulation with the administered medicine. The risk of these events occurring with the topically acting Jorveza is anticipated to be lower, relative to systemically acting glucocorticoids, consistent with the extensive biotransformation of budesonide and lower systemic absorption (see Section 5.2 Pharmacokinetic Properties).

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 a cataract, glaucoma or rare ocular diseases such as central serous chorioretinopathy (CSCR) which have been reported after use of systemic and topical glucocorticoids.

Angioedema.

Cases of angioedema and/or contact dermatitis have been reported with the use of Jorveza, mostly as part of an allergic reaction which include rash and itching. Treatment with Jorveza should be stopped if a patient develops swelling of the face, particularly around the mouth (lips, tongue or throat) and/or difficulties to breathe or swallow.

Others.

Glucocorticosteroids may cause suppression of the hypothalamic-pituitary-adrenal (HPA) axis and reduce the stress response. When patients are subject to surgery or other stresses, supplementary systemic glucocorticoid treatment is therefore recommended. It is unclear whether this supplementary treatment would be required for a patient receiving Jorveza owing to the low systemic absorption of budesonide (see Section 5.2 Pharmacokinetic Properties).
Concomitant treatment with ketoconazole or other CYP3A4 inhibitors should be avoided in patients receiving glucocorticoids (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Effects on laboratory tests.

No data available.

Interference with serological testing.

Because adrenal function may be suppressed by treatment with a glucocorticoid, especially one which is systemically acting, an ACTH stimulation test for diagnosing pituitary insufficiency might show false results (low values).

Excipient with known effect.

The Jorveza 0.5 mg and 1 mg tablets each contain 26 mg of sodium. Therefore, the maximum daily dose of sodium intake from either strength is 52 mg per day if taken as recommended as either 2 x 0.5 mg tablet or 2 x 1 mg tablet (see Section 4.2 Dose and Method of Administration). This is equivalent to 2.6% of the WHO recommended maximum daily intake of 2 g sodium for an adult.

4.5 Interactions with Other Medicines and Other Forms of Interactions

CYP3A4 inhibitors.

While no formal drug interaction studies have been conducted with Jorveza, based on studies with budesonide administered in enteric capsules, concomitant treatment with potent CYP3A inhibitors such as ketoconazole, ritonavir, itraconazole, erythromycin, clarithromycin, cobicistat and grapefruit juice may cause a marked increase of the plasma concentration of budesonide and is expected to increase the risk of systemic adverse reactions. Therefore, concomitant use should be avoided unless the benefit outweighs the increased risk of systemic glucocorticoid adverse reactions, in which case, patients should be monitored for systemic glucocorticoid adverse reactions.
Ketoconazole 200 mg once daily orally increased the plasma concentration of budesonide (single dose of a 3 mg budesonide enteric capsule) approximately 6-fold during concomitant administration. When ketoconazole was administered approximately 12 hours after the budesonide capsule, the plasma concentration of budesonide increased approximately 3-fold.

Oestrogens, oral contraceptives.

Elevated plasma concentrations and enhanced effects of glucocorticoids have been reported in women also receiving oestrogens or oral contraceptives. No such effect has been observed with budesonide and concomitant intake of low-dose combination oral contraceptives.

Cardiac glycosides.

The action of glycoside can be potentiated by potassium deficiency which is a potential and known adverse reaction of glucocorticoids.

Saluretics.

Concomitant use of glucocorticoids may result in enhanced potassium excretion and aggravated hypokalaemia.

Drug food interactions.

Inhibitors of CYP3A4 such as grapefruit juice may cause a marked increase of the plasma concentration of budesonide. In the absence of specific data for Jorveza concomitant use should be avoided.

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 of 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 Jorveza. There are few data of 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 in the treatment with Jorveza compared to inhaled budesonide. In pregnant animals, budesonide, like other glucocorticoids, has been shown to cause abnormalities of foetal development (smaller litter size, intrauterine growth retardation of foetuses and skeletal and visceral abnormalities). Some glucocorticoids have been reported to produce cleft palate in animals. The clinical relevance of these findings to humans has not been established.
 There is currently no experience with the administration of Jorveza in breast-feeding mothers. However, budesonide is known to be excreted in human milk when administered by inhalation. In the absence of specific experience, a decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Jorveza therapy, taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

4.7 Effects on Ability to Drive and Use Machines

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

4.8 Adverse Effects (Undesirable Effects)

Summary of the safety profile.

Fungal infections in the mouth, pharynx and the oesophagus were the most frequently observed adverse reactions in clinical studies with Jorveza. In the clinical studies, BUL-1/EEA and BUL2/EER, a total of 44 out of 268 patients (16.4%) exposed to Jorveza experienced cases of suspected fungal infections associated with clinical symptoms, which were all of mild or moderate intensity and which did not interfere with their daily activities. The total of 92 infections (including those without symptoms diagnosed by endoscopy and histology through proactive investigation required in the study protocol) was reported in 72 of 268 patients (26.9%). The frequency of the fungal infections was not dose-related. All patients received oral antifungal treatment or no medical intervention. None of the patients needed to cease or otherwise modify their Jorveza regimen due to a local fungal infection during the two studies, including while they received oral antifungal treatment.
Long-term treatment with Jorveza for up to 3 years (6-12 weeks of induction treatment followed by 48-weeks of maintenance treatment, with a further 96-weeks of open-label treatment) did not increase the rate of adverse effects observed, including local candidiasis or abnormally low morning serum cortisol levels.

Tabulated list of adverse reactions.

Adverse reactions observed in clinical studies with Jorveza are listed in Table 1, by MedDRA system organ class and frequency. Frequencies are defined as 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) or not known (cannot be estimated from the available data).
The following known adverse reactions of the therapeutic class (glucocorticoids), especially for those which are systemically acting, however, may also occur with the topically acting Jorveza (frequency = not known). See Table 2.

Post-market adverse reactions.

Adverse reactions seen with Jorveza during post-marketing surveillance.

Nervous system disorders.

Dysgeusia.

Reporting of suspected adverse reactions.

Reporting suspected adverse effects 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

For information on the management of overdose, contact the Poison Information Centre on 131126 (Australia).
In case of short-term overdose, no emergency medical treatment is required. There is no specific antidote. Subsequent treatment should be symptomatic and supportive.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Antidiarrheals, intestinal anti-inflammatory/anti-infective agents, glucocorticoids acting locally, ATC code: A07EA06.

Mechanism of action.

Budesonide is a non-halogenated glucocorticoid, which acts primarily as anti-inflammatory via binding to the glucocorticoid receptor. The exact mechanism of action in the treatment of EoE is not fully understood. In the treatment of EoE with Jorveza, budesonide may inhibit antigen-stimulated secretion of many pro-inflammatory signal molecules, which may result in a significant reduction of the oesophageal eosinophilic inflammatory infiltrate.

Pharmacodynamics.

The primary pharmacodynamic effect of budesonide is its anti-inflammatory activity. Budesonide has a high glucocorticoid effect and a weak mineralocorticoid effect, and the affinity of budesonide to glucocorticoid receptors, which reflects the intrinsic potency of the drug, is about 200-fold that of cortisol and 15-fold that of prednisolone.

Effect on hypothalamus-pituitary-adrenal and endogenous cortisol levels.

Treatment with systemically active glucocorticoid is associated with a suppression of endogenous cortisol concentrations and impairment of the HPA axis function.
Following 48 weeks of Jorveza 1 mg BID or 0.5 mg BID treatment in patients with EoE, the rate of patients with morning serum cortisol levels below the lower limit of normal (LLN) was 2.9% (4/136) for both Jorveza treatment regimens vs. 0% for the placebo group. None of these patients had symptoms of adrenal insufficiency. This is consistent with the extensive biotransformation of budesonide and thus its low systemic absorption of budesonide when administered as Jorveza (see Section 5.2 Pharmacokinetic Properties).

Clinical trials.

In a randomised, placebo-controlled, double-blind phase III clinical study (BUL-1/EEA) in 88 adult patients with active symptomatic and histological EoE (randomisation rate: 2:1), Jorveza 1 mg BID for 6 weeks induced clinicohistologic remission (defined as peak of < 16 eosinophils/mm2 high power field (hpf); < 5 eos/hpf in oesophageal biopsies with no or only minimal symptoms of dysphagia or pain during swallowing on each day in week prior to week 6 visit) in 34 out of 59 patients (57.6%) versus 0/29 patients (0%) in the placebo-group (p < 0.0001). Open-label extension of the treatment with Jorveza 1 mg BID for a further 6 weeks in 23 Jorveza-treated patients without remission in the preceding double-blind phase increased the rate of patients with clinicohistologic remission to 84.7%.
In a randomised, placebo-controlled, double-blind phase III clinical study (BUL-2/EER) including 204 adult patients with EoE in clinicohistological remission, induced by prior treatment with Jorveza 1 mg BID, were randomised to treatment with Jorveza 1 mg BID, Jorveza 0.5 mg BID, or placebo (all given as orally disintegrating tablets) for 48 weeks (n=68 for all treatment groups). Primary endpoint was the rate of patients free of treatment failure, with treatment failure defined as clinical relapse (severity of dysphagia or pain during swallowing of ≥ 4 points on a 0-10 numerical rating scale, respectively), and/or histological relapse (peak of ≥ 48 eosinophils/mm2 hpf; > 15 eos/hpf), and/or food impaction requiring endoscopic intervention, and/or need of an endoscopic dilation, and/or premature withdrawal for any reason. Significantly more patients in the Jorveza 1 mg BID (75.0%) group and the Jorveza 0.5 mg BID (73.5%) group were free of treatment failure at week 48, compared to placebo (4.4%); p < 0.0001; both treatments. The median time to clinical relapse was 86 days for the placebo group, compared to over 330 days for the two Jorveza dose groups (p < 0.0001 versus placebo; both treatments).
The most stringent secondary endpoint "deep disease remission", i.e. deep clinical, deep endoscopic and histological remission, showed a clinically relevant higher efficacy in the Jorveza 1 mg BID group (52.9%) compared to the Jorveza 0.5 mg BID group (39.7%), indicating the utility of the higher dose of Jorveza to achieve and maintain deep disease remission.
At the end of the 48 week double-blind period in BUL-2/EER, all patients free of treatment failure were invited to enter an optional 96-week open-label phase, each receiving either Jorveza 0.5 mg BID, or Jorveza 1 mg BID, based on decision of the treating physician. More than 80% of the patients maintained clinical remission (defined as weekly Eosinophilic Esophagitis Activity Index-Pro ≤ 20) over the 96-week period, while only 2/166 patients (1.2%) experienced a food impaction. In addition, 40/49 patients (81.6%) maintained deep histological remission (0 eosinophils/mm2 hpf in all biopsies) from baseline of study BUL-2/EER to the end of treatment of the 96-week open-label period.
Over a period of up to 3 years (i.e. 96-week open-label treatment with Jorveza, following the 48 week randomised, double-blind maintenance treatment and the preceding 6-12 week induction treatment with Jorveza), no loss of efficacy was observed.
For information about the observed adverse reactions, see Section 4.8 Adverse Effects (Undesirable Effects).

5.2 Pharmacokinetic Properties

Single doses and multiple doses of up to 4 mg/day were evaluated in the pharmacokinetic studies of the budesonide orally disintegrating tablets in healthy subjects and in patients with EoE. The results showed that systemic cumulative budesonide exposure after administration of the orally disintegrating tablets was lower than after the reference capsule (3 mg budesonide gastro-resistant capsule) while budesonide absorption was faster after the orally disintegrating tablets, relative to the reference capsule.

Absorption.

Following administration of Jorveza, budesonide is rapidly absorbed. Pharmacokinetic data following administration of single doses of a 1 mg budesonide orally disintegrating tablet to fasted healthy subjects in two different studies show a median lag time of 0.17 hours (range 0.00 - 0.52 hours) and a median time to peak plasma concentration of 1.00 - 1.22 hour (range 0.50 - 2.00 hours). The mean peak plasma concentration (± standard deviation) was 0.44 - 0.49 nanogram/mL (range 0.18 - 1.05 nanogram/mL) and the area under the plasma concentration-time curve (AUC0-∞) was 1.50 - 2.23 hr*nanogram/mL (0.81 - 5.14 hr*nanogram/mL).
Single dose pharmacokinetic data in fasted patients with EoE are also available with a 4 mg budesonide orally disintegrating tablet, with a median lag time of 0.00 hours (range 0.00 - 0.17 hours), median time to peak plasma concentration of 1.00 hour (range 0.67 - 2.00 hours); peak plasma concentration of 2.56 ± 1.36 nanogram/mL, and AUC0-12 of 8.96 ± 4.21 hr*nanogram/mL.
Patients with active EoE showed a 35% increase in peak plasma concentrations and a 60% increase in AUC0-12 compared to healthy subjects.
Dose proportionality of the systemic exposure (Cmax and AUC) from the 0.5 mg orally disintegrating tablets to the 1 mg budesonide orally disintegrating tablets has been demonstrated.
There was little to no accumulation of budesonide upon repeated dosing (daily 4 mg doses for 7 days) with the orally disintegrating tablets.

Distribution.

The apparent volume of distribution following oral administration of 1 mg budesonide orally disintegrating tablet to healthy subjects was 35.52 ± 14.94 L/kg and 42.46 ± 23.90 L/kg following administration of 4 mg budesonide orally disintegrating tablets to patients with EoE. Plasma protein binding is on average 85-90%.

Biotransformation.

Metabolism of budesonide is decreased in EoE patients with active disease compared to healthy subjects resulting in increased plasma concentrations of budesonide.
Budesonide undergoes extensive biotransformation by CYP3A4 in the mucosa of the small intestine and in the liver with only 10-15% of administered dose reaching the systemic circulation. The remaining proportion of the dose is transformed by CYP34A 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. CYP3A5 does not contribute significantly to the metabolism of budesonide. This is consistent with the low rate of systemic adverse events, including the absence of clinically relevant reductions in serum cortisol levels, in the clinical studies in EoE patients (see Section 5.1 Pharmacodynamic Properties).

Elimination.

The median elimination half-life is 2 - 3 hours in healthy subjects (receiving 1 mg budesonide orally disintegrating tablets) and 4 - 5 hours in EoE patients (receiving 4 mg budesonide orally disintegrating tablets). Clearance of budesonide is about 13 - 15 L/hour/kg in healthy subjects and 6.54 ± 4.4 L/hour/kg in EoE patients. Budesonide is eliminated by the kidney in marginal amounts, if at all. Budesonide was not detected in the urine; only budesonide metabolites were detected.

Hepatic impairment.

A relevant proportion of budesonide is metabolised in the liver by CYP3A4. The systemic exposure of budesonide is considerably increased in patients with severely impaired hepatic function. No studies have been conducted with Jorveza in patients with impaired liver function. In the absence of data, Jorveza should not be used in patients with hepatic impairment.

5.3 Preclinical Safety Data

Genotoxicity.

Budesonide had no mutagenic effects in a number of in vitro and in vivo tests.

Carcinogenicity.

The carcinogenic potential of budesonide has been assessed in mice and rats at respective oral doses of 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. As this was not confirmed in further studies in male Sprague-Dawley and Fischer rats, it was concluded that budesonide does not increase the incidence of brain tumours in rats. In male rats dosed with 10, 25 and 50 microgram/kg/day of budesonide, those receiving 25 and 50 microgram/kg/day regimens 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

Jorveza 0.5 mg and 1 mg orally disintegrating tablets.

Sodium acid citrate, docusate sodium, macrogol 6000, magnesium stearate, mannitol, sodium dihydrogen citrate, povidone, sodium bicarbonate, sucralose.

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

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

6.4 Special Precautions for Storage

Store below 25°C. Store in the original package in order to protect from light and moisture.

6.5 Nature and Contents of Container

Al/Al blister.

Jorveza 0.5 mg.

Pack sizes: 20, 60, 100 or 200 orally disintegrating tablets. Not all pack sizes may be marketed.

Jorveza 1 mg.

Pack sizes: 20, 30, 60 or 90 orally disintegrating tablets. Not all pack sizes may be marketed.

6.6 Special Precautions for Disposal

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Chemical structure.


Chemical name: 16α,17α-butylidene dioxy-11β,21-dihydroxy-1,4-pregnadiene-3,20-dione.
Molecular formula: C25H34O6.
Molecular mass: 430.5.

CAS number.

51333-22-3.
Physicochemical properties: Budesonide is a white or almost-white crystalline powder, with a pKa of 12.85 ± 0.10.
Budesonide is practically insoluble in water, freely soluble in methylene chloride, sparingly soluble in ethanol (96%).

7 Medicine Schedule (Poisons Standard)

Schedule 4 - Prescription Only Medicine.

Summary Table of Changes