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.

What is in this leaflet

This leaflet answers some common questions about JORVEZA tablets. 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 risk of you taking this medicine against the benefits it is expected to have for you.

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

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

What JORVEZA is used for

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.

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.

JORVEZA 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 take JORVEZA

When you must not take it

Do not take this medicine if you have an allergy to:

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

Some of the symptoms of an allergic reaction may include:

  • 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 take JORVEZA if you have uncontrolled infections or active tuberculosis.

Before you start to take 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 taking JORVEZA if you are pregnant or breastfeeding.

Tell your doctor if you have or have had any medical 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.

If you have not told your doctor about any of the above, tell him/her before you start taking JORVEZA tablets.

Tell your doctor if you are on other corticosteroid treatments.

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

Contact your doctor if you have been exposed to chicken pox, measles and shingles infections. These illnesses may become more severe when you take JORVEZA. JORVEZA treatment may need to be discontinued if you have one of these infections.

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.

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.

Tell your doctor if you 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.

If you know that you are due to have an operation please tell your doctor that you are taking JORVEZA.

If you 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.

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

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 used 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.

Taking other medicines

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

Some medicines and JORVEZA 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 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 may affect how well it works. You may need to take different amounts of your other medicine(s), or you may need to take different medicines.

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

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

How to take JORVEZA

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

How much to take

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.

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.

How to take it

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.

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 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 it

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 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 (overdose)

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

While you are taking JORVEZA

Things you must do

If you are about to start 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 must not do

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

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

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

Things to be careful of

Avoid drinking grapefruit juice. Grapefruit juice contains some components that influence the metabolism (break-down) of JORVEZA. This can worsen its side effects.

Side effects

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

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

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 if you notice any of the following that are troublesome or ongoing:

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 (symptoms can be white spots)

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.

When JORVEZA is taken, side effects may occur which are typical of the more active corticosteroid preparations (Cushing-like properties). The side effects listed below depend on the dose, the period of JORVEZA treatment, whether there has been prior or accompanying treatment with other corticosteroid preparations and on the individual sensitivity.

  • 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.

If any of the following happen, stop taking JORVEZA and tell your doctor immediately, or go to Accident and Emergency at your nearest hospital:

  • swelling of the face, particularly of the eyelids, lips, tongue or throat (angioedema)
  • shortness of breath
  • itchy rash or hives.

These are the symptoms of an allergic reaction.

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

Tell your doctor or pharmacist if you notice anything that is making you feel unwell.

Other side effects not listed above may also occur in some people.

After taking JORVEZA

Storage

Keep JORVEZA in the original container.

JORVEZA tablets should not be removed from the individual blisters until immediately before dosing.

If you take it out of its container it may not keep well.

Keep JORVEZA in a cool dry place where the temperature stays below 25°C. Protect from light and moisture.

Do not store JORVEZA 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, including JORVEZA.

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

Disposal

If your doctor tells you to stop taking JORVEZA or the expiry date has passed, ask your pharmacist or doctor what to do with any medicine that is left over.

Product description

What it 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

Ingredients

Active ingredients:

JORVEZA 1 mg orally disintegrating tablets – 1 mg budesonide

JORVEZA 0.5 mg orally disintegrating tablets – 0.5 mg budesonide

Inactive ingredients:

  • magnesium stearate
  • sodium acid citrate
  • sodium dihydrogen citrate
  • docusate sodium
  • sucralose
  • sodium bicarbonate
  • mannitol
  • macrogol 6000
  • povidone

Supplier

JORVEZA® is supplied in Australia by:

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

This leaflet was prepared in April 2024.

Australian Register Number

JORVEZA 1 mg orally disintegrating tablets:
AUST R 322645

JORVEZA 0.5 mg orally disintegrating tablets
AUST R 350996

Published by MIMS June 2024

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