Active ingredients: Budesonide
Budexan 0.25 mg / ml suspension for nebulisation
Budexan 0.5 mg / ml suspension for nebulisation
Why is Budexan used? What is it for?
Budexan contains the active substance budesonide.
Budexan belongs to a group of medicines called glucocorticosteroids which are hormones that perform numerous activities, with an important function in controlling inflammation.
Budexan is indicated in the treatment of the following diseases:
- an inflammatory disease characterized by obstruction of the bronchi (bronchial asthma);
- a disease characterized by an obstruction of the throat (larynx) which makes it difficult for air to pass through and for which hospitalization is indicated (very severe subglottic laryngitis (pseudocroup)).
Contraindications When Budexan should not be used
Do not take Budexan if you are allergic to the active substance or any of the other ingredients of this medicine.
Precautions for use What you need to know before taking Budexan
Talk to your doctor or pharmacist before taking Budexan if:
- have reduced liver function;
- you are taking ketoconazole (a medicine to treat fungal diseases) or HIV protease inhibitors (medicines to treat AIDS) or other inhibitors of cytochrome CYP3A4 (the enzyme most involved in the breakdown of medicines) at the same time;
- have active or quiescent pulmonary tuberculosis or have fungal or viral infections of the respiratory tract;
- have fungal and virus infections (measles and chickenpox);
- has glaucoma (characterized by chronic damage to the nerve of the eye) and cataracts (loss of transparency of a part of the eye called the lens).
Budexan does not give rapid improvement in sudden (acute) episodes of asthma, for which other types of medicines such as short-acting bronchodilators need to be used.
Your doctor must carefully evaluate whether you have not benefited from the use of short-acting bronchodilators, in which case he may decide to increase the number of budesonide inhalations compared to the usual one or to start therapy with oral glucorticosteroids. .
In these two cases, the doctor must evaluate the possible risks of compromise and / or insufficiency of a gland called the adrenal gland.
The doctor must carefully evaluate the suspension from treatment with oral glucocorticosteroids as rare cases of general malaise may occur such as muscle and joint pain, tiredness, headache (headache), depression, nausea and vomiting although it may have an improvement in lung function.
The replacement of treatment with glucocorticosteroids that are distributed throughout the body (systemic) with inhaled therapy can sometimes lead to allergies, such as inflammation of the nose (rhinitis) and skin (eczema).
A fungal disease called oral candidiasis may develop during inhaled therapy. This infection may require treatment with appropriate antifungal therapy and in some cases treatment may need to be stopped (see section "How to take Budexan").
In long-term treatment, local and whole-body effects may occur with high doses of Budexan (Cushing's syndrome, Cushingoid aspect, adrenal suppression, decreased bone mineral density, cataract, glaucoma, rarely psychological and behavioral effects including hyperactivity psychomotor, sleep disturbances, anxiety, depression, aggression, behavioral disturbances).
Once your asthma has been controlled, your doctor will prescribe the lowest effective maintenance dose. Do not increase or decrease your dose without first consulting your doctor.
Similarly to what happens with other therapies administered by inhalation, it can have a contraction of the bronchi (paradoxical bronchospasm) with an immediate increase in breathing difficulty (wheezing) after administration. In this case, you should immediately stop taking inhaled budesonide and your doctor will evaluate the situation and alternative therapy if necessary.
Children and adolescents
Budexan should be used with caution in children.
Influence on growth
Height should be checked periodically if you have a child on prolonged treatment with inhaled glucocorticosteroids. If growth is slowed, your doctor will consider reducing the dose of the medicine. The benefits of therapy and the possible risk of growth suppression should be done. be carefully evaluated by the doctor who can refer the child to a pediatric pulmonologist specialist.
Behavioral disturbances may occur in long-term treatment with high doses of Budexan.
Interactions Which drugs or foods may change the effect of Budexan
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
No interactions of budesonide have been observed with any other medicinal product used in the treatment of asthma.
You must avoid taking it at the same time or you must allow as long an interval of time as possible between treatments if you have to take:
- ketoconazole and itraconazole, medicines to treat fungal diseases, as they can increase the amount of budesonide in the body (see section "Warnings and precautions"). Your doctor may also consider reducing the dose of Budexan.
Budexan interferes with:
- estrogens and hormones used in contraceptive pills because in these cases the amount of budesonide in the blood increases with the consequent effects on the organism. No effect has been observed with the use of budesonide and the concomitant intake of low-dose oral contraceptives.
Budexan can alter the results of some laboratory tests used to diagnose "insufficient activity of a gland called the pituitary gland (ACTH stimulation test to diagnose" pituitary insufficiency may give false results for detecting low values).
Warnings It is important to know that:
Pregnancy and breastfeeding
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.
Pregnancy
Inhaled budesonide did not show any adverse health effects on the fetus / newborn during pregnancy. During pregnancy, your doctor will evaluate the expected benefits for you against the risks to the fetus.
Feeding time
Budesonide can pass into breast milk. No effects on the suckling child are expected at therapeutic doses of Budexan. Budesonide can be used during breastfeeding.
Driving and using machines
Budexan does not affect the ability to drive and use machines.
Dosage and method of use How to use Budexan: Dosage
Always take this medicine exactly as your doctor or pharmacist has told you.
If in doubt, consult your doctor or pharmacist.
Bronchial asthma
Adults and the elderly
Initial dose:
Budexan dosage is individual.
The recommended starting dose is 0.5-1 mg twice a day.
In cases where a greater therapeutic effect is required, higher doses of Budexan may be prescribed.
Maintenance dose:
The maintenance dose is individual.
Once the desired clinical results are obtained, the doctor will reduce the dose until the minimum amount necessary to control symptoms is reached.
Onset of effect
Improvement of asthma control following administration of Budexan may occur within 3 days of starting treatment, although maximum benefit is obtained after 2 to 4 weeks.
Patients treated with oral glucocorticosteroids (see section "Warnings and precautions")
Budexan may allow for replacement or significant reduction in oral glucocorticosteroid dosage while maintaining asthma control.
Your doctor will consider how to switch from oral glucocorticosteroid therapy to treatment with Budexan Nebuliser Suspension.
Splitting the dose and mixing
Your doctor may ask you to mix Budexan with 0.9% saline and other solutions containing medicines that affect the breath such as terbutaline, salbutamol, fenoterol, acetylcysteine, sodium cromoglycate or ipratroprium bromide.
The mixture should be used within 30 minutes.
The contents of the single-dose container can be divided to allow for dosage adjustment.
A line is clearly visible on the single-dose containers of Budexan.
When the single-dose container is held upside down, the line indicates a volume of 1 ml.
If only 1 ml is to be used, empty the contents of the single-dose container until the liquid surface reaches the indicated line.
Before using the remaining liquid, shake the contents carefully with a twisting motion.
DOSAGE TABLE
* The medicinal product must be mixed with 0.9% physiological solution to reach the volume of 2 ml.
Use in children and adolescents
Bronchial asthma
Children aged 6 months and over up to 12 years
Total recommended daily dose is 0.25-0.5 mg.
If you have a child on oral glucocorticosteroids, your doctor may decide to start with a higher starting total daily dose, for example 1 mg.
The doctor will consider the higher dose (2 mg per day) only in children with severe asthma and for limited periods.
Subglottic laryngitis (throat obstruction)
The recommended dose is 2 mg of Budexan which can be given as a single dose or as two 1 mg doses 30 minutes apart.
Dosing can be repeated every 12 hours for up to 36 hours or until clinical improvement.
It is advisable for children to use a perfectly tight and well-fitting face mask, capable of optimizing the administered dose of budesonide.
INSTRUCTIONS FOR THE CORRECT USE OF BUDEXAN
Note:
Nebulization time and the amount of medicine delivered by a nebulizer depend on the flow rate of the compressor and the fill volume.
Due to the small delivered amount of budesonide, ultrasonic nebulizers should not be used to administer Budexan.
Gently shake the vial with a twisting motion.
Hold the single-dose container upright and open by rotating the flap until the container opens.
Place the open end of the single-dose container well into the nebulizer tank and press slowly.
Rinse the mouth with water after each administration in order to reduce the occurrence of fungal infections (oropharyngeal thrush). If a face mask is used, it must be ensured that the mask adheres well during spraying. After using the face mask, wash your face with water to prevent irritation.
Cleaning:
The nebulizer chamber should be cleaned after each administration. Wash the nebulizer chamber and mouthpiece or face mask in warm tap water using a mild detergent or follow the manufacturer's instructions. Rinse well and dry the chamber by rejoining the compressor and inhaler.
If you forget to take Budexan
Do not take a double dose to make up for a forgotten dose.
If you stop taking Budexan
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
Overdose What to do if you have taken too much Budexan
Acute overdose with Budexan, even in high doses, should not cause clinical problems. If you accidentally take an overdose of Budexan, notify your doctor immediately or go to the nearest hospital.
Side Effects What are the side effects of Budexan
Like all medicines, this medicine can cause side effects, although not everybody gets them. The following side effects have been observed:
Common (may affect more than 1 in 100 people)
- fungal infections in the mouth and throat (Candida in the oropharynx);
- nausea;
- cough, hoarseness, throat irritation.
Rare (may affect up to 1 in 1,000 people)
- immediate or delayed hypersensitivity reactions including rash with pustules, blisters and blisters (rash), inflammation of the skin due to contact with certain substances (contact dermatitis), sudden onset of a more or less itchy rash (hives), rapid swelling of the skin and mucous membranes (angioedema) and severe and sudden allergic reaction (anaphylactic reaction);
- suppression of the activity of a gland called the adrenal gland;
- restlessness, nervousness, depression, behavioral changes, sleep disturbances, anxiety, psychomotor hyperactivity, aggression;
- bruises, skin streaks.
Not known (frequency cannot be estimated from the available data)
- chronic damage to the nerve of the eye (glaucoma), loss of transparency of a part of the eye called the lens (cataract).
Rarely, for unknown mechanisms, inhaled medicinal products can cause bronchospasm.
To prevent irritation, the facial skin should be washed with water after using the face mask.
Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects.
Additional side effects in children and adolescents
Rare (may affect up to 1 in 1,000 people)
- growth retardation;
- psychomotor hyperactivity, aggression;
- bronchospasm with voice disturbances (dysphonia and hoarseness).
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system at www.agenziafarmaco.it/it/responsabili. By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
Do not store above 25 ° C.
Store in the original package to protect the medicine from light.
After opening the aluminum bag, the single-dose containers must be used within 3 months. After this time the residual product must be discarded.
After opening the foil pouch, unused single-dose containers must be kept in the pouch, protected from light.
The opened single-dose container must be used within 12 hours. After this time, the residual product must be eliminated.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton after "Expiry".
The expiry date refers to the last day of that month.
Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Other information
What Budexan contains
Budexan 0.25 mg / ml suspension for nebulisation
- The active ingredient is budesonide. 1 single-dose container contains 0.5 mg of budesonide.
- The other ingredients are disodium edetate, sodium chloride, polysorbate 80, anhydrous citric acid, sodium citrate, water for injections.
Budexan 0.5 mg / ml suspension for nebulisation
- The active ingredient is budesonide. 1 single-dose container contains 1 mg of budesonide.
- The other ingredients are disodium edetate, sodium chloride, polysorbate 80, anhydrous citric acid, sodium citrate, water for injections.
What Budexan looks like and contents of the pack
Suspension to be sprayed.
Each package contains 20 single-dose containers divided into strips of 5 units contained in an aluminum bag.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
BUDEXAN SUSPENSION TO NEBULIZE
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
1 single-dose container contains:
active ingredient: budesonide 0.5 mg
BUDEXAN 0.5 mg / ml suspension for nebulisation
1 single-dose container contains:
active ingredient: budesonide 1 mg
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Suspension to be sprayed
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
BUDEXAN Nebuliser Suspension is indicated for the treatment of bronchial asthma.
BUDEXAN Nebuliser Suspension is also indicated in the treatment of very severe subglottic laryngitis (pseudocroup) where hospitalization is indicated.
04.2 Posology and method of administration
Bronchial asthma:
Initial dose:
The dosage of BUDEXAN Suspension to be nebulised is individual.
The starting dose should be:
Children aged 6 months and over and up to 12 years:
Total daily dose of 0.25-0.5 mg. In patients on oral steroid therapy, it is possible to start with a higher initial total daily dose, for example 1 mg. The higher dose (2 mg per day) should only be considered in children with severe asthma and for limited periods.
Adults and the elderly:
0.5-1 mg twice a day. If necessary, the dose can be further increased.
In cases where a greater therapeutic effect is required, it is possible to administer higher doses of BUDEXAN Suspension to be nebulised; in fact the risks of systemic effects are low, if compared with those detectable following a treatment in combination with oral glucocorticosteroids.
Maintenance dose:
The maintenance dose is individual.
Once the desired clinical results are achieved, the maintenance dose should be gradually reduced until the minimum amount necessary to control symptoms is achieved.
Onset of effect:
Improvement in asthma control following administration of inhaled BUDEXAN Nebuliser Suspension may occur within 3 days of starting treatment, although maximum benefit is obtained after 2-4 weeks.
Patients treated with oral steroids (see also 4.4):
BUDEXAN Nebuliser Suspension may allow for replacement or significant reduction of oral steroid dosage while maintaining asthma control.
When initiating the transfer from oral corticosteroid therapy to BUDEXAN Nebuliser Suspension, the patient should be in a relatively stable phase. A high dose of BUDEXAN Suspension to be nebulised. it is then administered in combination with the previously used oral dose for approximately 10 days.
After that, the oral steroid dose should be gradually reduced (e.g. from 2.5 milligrams of Prednisolone or equivalent each month) to the lowest possible level In many cases it is possible to completely replace the oral steroid with BUDEXAN Nebuliser suspension .
Splitting the dose and mixing:
BUDEXAN Nebuliser suspension can be mixed with 0.9% saline and nebulisation solutions of terbutaline, salbutamol, fenoterol, acetylcysteine, sodium cromoglycate or ipratroprium bromide.
The mixture should be used within 30 minutes.
The contents of the single-dose container can be divided to allow for dosage adjustment.
A line is clearly visible on the single-dose containers of BUDEXAN Suspension to be nebulized. When the single-dose container is held upside down, the line indicates a volume of 1 ml. If only 1 ml is to be used, empty the contents of the single-dose container until the liquid surface reaches the indicated line.
Before using the remaining liquid, shake the contents carefully with a twisting motion.
DOSAGE TABLE
* The product must be mixed with 0.9% physiological solution to reach the volume of 2 ml.
Subglottic laryngitis
In infants and children with subglottic laryngitis the usual dose is 2 mg of BUDEXAN Nebuliser Suspension which can be given as a single administration or as two 1 mg doses 30 minutes apart. The dosage can be repeated every 30 minutes. 12 hours for up to 36 hours or until clinical improvement.
INSTRUCTIONS FOR THE CORRECT USE OF BUDEXAN SUSPENSION TO NEBULIZE
Gently shake the single-dose container with a twisting motion.
Hold the single-dose container upright and open by rotating the flap until the container opens.
Place the open end of the single-dose container well into the nebulizer tank and press slowly.
Note:
Rinse the mouth with water after each administration in order to reduce the appearance of oropharyngeal thrush.
If a face mask is used, it must be ensured that the mask adheres well during spraying. After using the face mask, wash your face with water to prevent irritation.
Cleaning:
The nebulizer chamber must be cleaned after each administration. Wash the nebulizer chamber and mouthpiece or face mask in warm tap water using a mild detergent or follow the manufacturer's instructions. Rinse well and dry the chamber by rejoining the compressor and inhaler.
Nebulization time and the amount of drug delivered by a nebulizer depend on the flow rate of the compressor and the fill volume.
In vitro the quantity of budesonide delivered by the nebulizer varies between 30-70% of the nominal dose, depending on the type of nebulizer and compressor used and not all nebulizers and compressors are suitable for the use of BUDEXAN Suspension to be nebulized.
To obtain the maximum budesonide delivery, a compressor is required that guarantees a flow of 5 to 8 liters / min and a filling volume of 2-4 ml.
Studies performed in vivo have shown that the dose of nebulised budesonide administered to patients varies between 11 and 22% of the nominal dose.
It is advisable for children to use a perfectly tight and well-fitting face mask, capable of optimizing the administered dose of budesonide.
Due to the small delivered amount of budesonide, ultrasonic nebulizers should not be used to administer BUDEXAN Nebuliser Suspension.
04.3 Contraindications
Hypersensitivity to budesonide or to any of the excipients.
04.4 Special warnings and appropriate precautions for use
BUDEXAN Nebuliser Suspension is not intended for the rapid improvement of acute episodes of asthma, for which a short-acting bronchodilator is required. The physician must carefully evaluate the cases of patients who do not benefit from the use of short-acting bronchodilators or who increase the number of inhalations compared to the usual one. In these cases, the physician should evaluate the need for increased therapy with anti-inflammatory drugs, for example by increasing the dose of inhaled budesonide or by starting a course of oral glucocorticosteroid therapy.
Particular attention should be paid to transferring patients from oral steroid therapy as the risk of adrenal compromise may remain for a long period of time. Patients who have required emergency therapy with high doses of corticosteroids or prolonged treatment with high doses of inhaled corticosteroids may also be at risk. Such patients may show signs and symptoms of adrenal insufficiency when exposed to severe stress. In times of stress or in the case of elective surgery, additional coverage with systemic corticosteroid should be considered. During the suppression phase of systemic glucocorticosteroid therapy some patients may experience general malaise such as muscle and joint pain. General glucocorticosteroid insufficiency should be suspected in the rare cases of onset of symptoms such as fatigue, headache, nausea and vomiting. In these cases, a temporary increase in the oral glucocorticosteroid dose may sometimes be necessary.
Some patients may experience symptoms of systemic glucocorticosteroid suppression, such as joint and / or muscle pain, fatigue and depression despite maintaining or even improving lung function during the period of withdrawal of oral steroid treatment. Such patients should be encouraged to continue therapy with BUDEXAN Nebuliser Suspension but should be monitored for objective signs of adrenal insufficiency. If there is evidence of adrenal insufficiency, the dose of the systemic corticosteroid should be temporarily increased and the transfer to BUDEXAN Nebuliser Suspension may be continued later, more slowly. During times of stress or during a severe asthma attack, patients who are replacing systemic steroid treatment with inhaled therapy may need additional systemic corticosteroid treatment.
Replacing systemic steroid treatment with inhaled therapy can sometimes manifest allergies, such as rhinitis and eczema, previously controlled by systemic steroid treatment. These allergic manifestations should be symptomatically controlled with antihistamine drugs and / or topical preparations.
Reduced liver function affects the elimination of glucocorticosteroids, resulting in a reduced elimination rate and higher systemic exposure. This may be clinically relevant in patients with severely impaired hepatic function.
It is necessary to be aware of possible systemic side effects.
The concomitant use of ketoconazole, HIV protease inhibitors or other potent CYP3A4 inhibitors should be avoided. If this is not possible, the time period between the two treatments should be as long as possible (see also section 4.5).
Special caution is required in the case of patients with active or quiescent pulmonary tuberculosis and in patients with fungal or viral infections of the respiratory tract.
BUDEXAN should be used with caution in patients with fungal and viral infections (such as measles and chickenpox) and in those with glaucoma and cataracts.
Oral candidiasis may occur during inhaled corticosteroid therapy. This infection may require treatment with appropriate antifungal therapy and treatment may need to be stopped in some patients (see also 4.2).
Systemic effects may occur with inhaled corticosteroids, particularly when prescribed in high doses for prolonged periods. These effects are less likely to occur than with oral corticosteroid treatment. Possible systemic effects include Cushing's syndrome, Cushingoid aspect, adrenal suppression, growth retardation in children and adolescents, decreased bone mineral density, cataracts, glaucoma and, more rarely, a range of psychological or behavioral effects including psychomotor hyperactivity, disturbances sleep, anxiety, depression or aggression (particularly in children). It is therefore important that the dose of the inhaled corticosteroid be the lowest possible dose with which effective control of asthma is maintained.
Therefore, on the basis of the above, once asthma control has been achieved, the dose to be used in maintenance treatment should be the least effective.
BUDEXAN should be used with caution in children.
As with other inhaled therapies, paradoxical bronchospasm may arise with an immediate increase in wheezing after administration. If this occurs, inhaled budesonide should be discontinued immediately, the patient should be evaluated and alternative therapy initiated if necessary.
Influence on growth
It is recommended that the height of children on prolonged treatment with inhaled corticosteroids is periodically monitored. If growth is slowed, therapy should be re-evaluated in order to reduce the dose of inhaled corticosteroids. The benefits of therapy with corticosteroids. and the possible risk of growth suppression should be carefully considered, and consideration should be given to referring the patient to a pediatric pulmonologist specialist.
04.5 Interactions with other medicinal products and other forms of interaction
No interactions of budesonide have been observed with any other drug used in the treatment of asthma.
The metabolism of budesonide is mainly mediated by CYP3A4, the cytochrome p450 isoenzyme. Inhibitors of this enzyme, such as ketoconazole and itraconazole, can therefore increase systemic exposure to budesonide by several fold (see 4.4). Given the lack of data to support a dosage recommendation, the combination of these drugs should be avoided. If this is not possible, the length of time between the two treatments should be as long as possible and a reduction in the dose of budesonide may also be considered.
Based on a limited amount of data regarding this interaction for high doses of budesonide administered by the inhaled route, substantial increases in plasma levels (on average four-fold) may occur when itraconazole, 200 mg once daily, is administered. concomitantly with inhaled budesonide (single dose equal to 1000 mcg).
Elevated plasma concentrations and enhanced effects of corticosteroids were observed in women also treated with estrogen and contraceptive steroids, while no effect was observed with the use of budesonide and the concomitant intake of low-dose oral contraceptives.
Since adrenal gland function may be inhibited, an ACTH stimulation test to diagnose "pituitary insufficiency may give false (low values) results."
At recommended doses, cimetidine has a slight effect on the pharmacokinetics of orally administered budesonide which is not clinically relevant.
04.6 Pregnancy and breastfeeding
The results from large prospective epidemiological studies and post-marketing experience on a worldwide scale do not indicate any adverse effects on the health of the fetus / neonate with the use of inhaled budesonide during pregnancy.
As with other drugs, the expected benefits to the mother should be weighed against the risks to the fetus when administering budesonide during pregnancy. Budesonide is excreted in breast milk. However, no effects on the suckling child are expected at therapeutic doses of budesonide. Budesonide can be used during lactation. Maintenance therapy with inhaled budesonide (200 or 400 mcg twice daily) in breastfeeding asthmatic women results in negligible systemic exposure to budesonide in breastfed infants.
In a pharmacokinetic study, the estimated daily dose for the infant was 0.3% of the daily dose taken by the mother for both dose levels and the mean plasma concentrations in the infant were estimated to be 1/600 of the concentrations observed in maternal plasma, assuming complete oral bioavailability for the infant. Budesonide concentrations found in infant plasma samples were always found to be below the limit of quantification.
Based on data obtained with the use of inhaled budesonide and on the fact that budesonide exhibits a linear pharmacokinetic profile within the therapeutic dose range after nasal, inhaled, oral and rectal administration at the therapeutic doses of budesonide, l " infant exposure is presumably low.
04.7 Effects on ability to drive and use machines
BUDEXAN Nebuliser suspension does not affect the ability to drive and use machines.
04.8 Undesirable effects
Clinical trials, literature and marketing experience suggest that the following adverse reactions may occur.
Frequencies are defined as: very common (≥ 1/10), common (≥ 1/100 to
* refer to "Description of selected adverse reactions"; facial skin irritation, listed below.
** refer to the "Pediatric Population" section below.
Rarely, for unknown mechanisms, drugs administered by inhalation can cause bronchospasm.
With inhaled administration of glucocorticosteroids, signs and symptoms of systemic glucocorticosteroid effects may rarely occur including adrenal hypofunctionality and decreased rate of growth which are likely to depend on dose, exposure time, concomitant and previous steroid treatment and sensitivity. individual.
Description of selected adverse reactions
Facial skin irritation as an example of a hypersensitivity reaction has appeared in some cases where a nebulizer with mask was used. To prevent irritation, the facial skin should be washed with water after using the face mask.
Patients recently diagnosed with chronic obstructive pulmonary disease (COPD) who start treatment with inhaled corticosteroids are at increased risk of developing pneumonia. However, a weighted evaluation of 8 pooled clinical trials conducted in 4643 patients with COPD and treated with budesonide and 3643 patients randomized to treatments without inhaled corticosteroids found no increased risk of developing pneumonia. The results of the first 7 of these 8 clinical studies were published in a meta-analysis.
Pediatric population
Given the risk of growth retardation in the pediatric patient population, growth should be monitored as described in section 4.4.
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "address: www.agenziafarmaco.gov.it/it/responsabili.
04.9 Overdose
Acute overdose with BUDEXAN Nebuliser Suspension, even in high doses, is not expected to cause clinical problems.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: other antihistamines, inhalers, glucocorticoids.
ATC code: R03BA02
Local anti-inflammatory activity
The exact mechanism of action of glucocorticosteroids in the treatment of asthma is not fully understood. The anti-inflammatory activity directed against T cells, eosinophils and mast cells, as well as the inhibition of the release of inflammatory mediators and the inhibition of the immune response mediated by cytokines are probably important. The intrinsic potency of budesonide, measured as affinity in comparisons of glucocorticoid receptors, is approximately 15 times higher than that of prednisolone.
A clinical study in asthmatic patients, in which inhaled budesonide was compared to oral administration at similar plasma concentrations, demonstrated "evidence of statistically significant efficacy with inhaled but not with inhaled administration. oral administration, compared to placebo. Therefore, the therapeutic effect of conventional doses of budesonide, administered by inhalation, can be largely attributed to local action in the respiratory tract.
In provocative studies, conducted in animals and patients, budesonide has been shown to have an anti-anaphylactic and anti-inflammatory effect, represented by the reduction of the degree of bronchial obstruction in the immediate and late allergic response.
Respiratory Tract Reactivity:
In hyperreactive patients, budesonide has been shown to reduce airway reactivity to histamine and methacholine.
Influence on plasma cortisol concentrations:
Studies with budesonide in healthy volunteers have shown dose-related effects on plasma and urinary cortisol. The ACTH test showed that budesonide treatment, at recommended dosages, produced significantly less effects on adrenal function than prednisone 10 mg.
Pediatric population
Clinic - asthma
The efficacy of budesonide has been evaluated in a large number of studies, and budesonide has been shown to be effective in both adults and children, as a prophylactic treatment of persistent asthma once or twice daily. Some examples of representative studies are reported. below.
Clinic - laryngotracheobronchitis
A series of studies in children with laryngotracheobronchitis compared budesonide with placebo. Examples of representative studies evaluating the use of budesonide for the treatment of children with laryngotracheobronchitis are given below.
Efficacy in children with mild to moderate laryngotracheobronchitis
A randomized, double-blind, placebo-controlled study was conducted in 87 children (7 months to 9 years), hospitalized with a clinical diagnosis of laryngotracheobronchitis, to determine whether budesonide improves the laryngotracheobronchitis symptom score or reduces the length of hospital stay. An initial dose of budesonide (2 mg) or placebo was followed by budesonide 1 mg or placebo every 12 hours. Budesonide statistically significantly improved the laryngotracheobronchitis score at 12 and 24 hours and 2 hours in patients with an initial laryngotracheobronchitis symptom score greater than 3. C "was also a 33% reduction in length of stay.
Efficacy in children with moderate to severe laryngotracheobronchitis
A randomized, double-blind, placebo-controlled study compared the efficacy of budesonide and placebo in the treatment of laryngotracheobronchitis in 83 infants and children (aged 6 months to 8 years) admitted to hospital for laryngotracheobronchitis. Patients received budesonide 2 mg or placebo every 12 hours for up to 36 hours or until hospital discharge. The total laryngotracheobronchitis symptom score was assessed at 0, 2, 6, 12, 24, 36, and 48 hours after the initial dose. At 2 hours, both the budesonide group and the placebo group showed similar improvement in the laryngotracheobronchitis symptom score, with no statistically significant differences between the groups. By 6 hours, the laryngotracheobronchitis symptom score in the budesonide group improved statistically significantly compared to the placebo group, and this improvement compared to placebo was equally evident at 12 and 24 hours.
05.2 Pharmacokinetic properties
Absorption
In adults, the systemic bioavailability of budesonide after administration of the suspension to be nebulised via a jet nebulizer is approximately 15% of the nominal dose and 40-70% of the dose delivered to patients. A minor fraction of the drug's systemic availability comes from ingested drug. After administration of a single dose of 2 mg, the maximum plasma concentration, which is reached approximately 10-30 minutes after the start of nebulization, is 4 nmol / l.
Distribution
Budesonide has a volume of distribution of approximately 3 L / kg. Plasma protein binding is, on average, 85-90%.
Biotransformation
First pass hepatic budesonide is rapidly metabolised in a high percentage (> 90%) to metabolites characterized by a low glucocorticosteroid activity. The main metabolites are 6-beta-hydroxybudesonide and 16-alpha-hydroxyprednisolone, whose glucocorticosteroid activity is less than 1% compared to that of budesonide. The metabolism of budesonide is mainly mediated by the isoenzyme CYP3A4, belonging to the cytochrome p450.
Elimination
The metabolites of budesonide are excreted as such or in conjugated form, mainly via the kidneys. Unchanged budesonide is not found in the urine. In healthy adults, budesonide has a high systemic clearance (approximately 1.2 L / min) and, after intravenous administration, the terminal half-life is, on average, 2-3 hours.
Linearity
At clinically relevant dosages, the kinetic parameters of budesonide are dose dependent.
Pediatric population
Budesonide has a systemic clearance of approximately 0.5 L / min in 4-6 year old asthmatic children. Children have a clearance per kg of body weight which is approximately 50% greater than in adults. The terminal half-life of budesonide after inhalation is approximately 2.3 hours in asthmatic children. This is approximately the same as in healthy adults.
After administration of the suspension to be nebulized, in asthmatic children aged 4-6 years, the systemic bioavailability of budesonide through a jet nebulizer (PARI LC Plus with Jet Pari Master compressor) is approximately 6% of the nominal dose and 26% of the dose delivered to patients. In children, the systemic bioavailability is approximately half that found in healthy adults. In 4-6 year old asthmatic children, after the administration of a 1 mg dose, the maximum plasma concentration, which is reached about 20 minutes after the start of nebulization, is equal to about 2.4 nmol / l.
In children 4-6 years of age, the exposure (Cmax and AUC) of budesonide following administration of a single 1 mg dose by nebulisation is comparable to that observed in healthy adults treated with the same dose using the same system. nebulization.
05.3 Preclinical safety data
The results of acute, subacute and chronic toxicity studies show that the systemic effects of budesonide are either less severe, or similar to those observed after administration of other glucocorticosteroids, for example, decreased weight gain, atrophy of lymphoid and adrenal tissues .
Budesonide, evaluated with six different tests, did not demonstrate any mutagenic or clastogenic effects.
The increase in the incidence of cerebral gliomas, found in a carcinogenicity study conducted in male rats, was not confirmed in two subsequent studies, in which the incidence of gliomas observed in the groups treated with active drugs (budesonide, prednisolone, triamcinolone acetate) was similar to that observed in the control groups.
Carcinogenicity studies conducted in male rats allowed to observe liver alterations (primary hepatocellular neoplasms) which were confirmed in another study carried out by treating animals with budesonide and reference glucocorticosteroids. These manifestations are probably related to receptor effects of glucocorticosteroids and represent an effect typical of the therapeutic class.
The available clinical experience shows that there is no evidence that budesonide, or other glucocorticosteroids, cause brain gliomas or primary hepatocellular neoplasms in humans.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Disodium edetate; sodium chloride; polysorbate 80; anhydrous citric acid; sodium citrate; water for injections.
06.2 Incompatibility
There are no known incompatibilities.
For compatible products, see section 4.2.
06.3 Period of validity
3 years.
06.4 Special precautions for storage
Store at a temperature not exceeding 25 ° C in the original packaging to protect the product from light.
After opening the aluminum bag, the single-dose containers must be used within 3 months. After this time the residual product must be discarded.
After opening the foil pouch, unused single-dose containers must be kept in the pouch, protected from light.
The opened single-dose container must be used within 12 hours. After this time, the residual product must be eliminated.
06.5 Nature of the immediate packaging and contents of the package
Single-dose container in low density polyethylene containing 2 ml of suspension.
Each package contains 20 single-dose containers divided into 5-unit strips contained in an aluminum bag.
06.6 Instructions for use and handling
See section 4.2
07.0 MARKETING AUTHORIZATION HOLDER
Genetic S.p.A., Via Della Monica n. 26, 84083 Castel San Giorgio (SA)
08.0 MARKETING AUTHORIZATION NUMBER
BUDEXAN 0.25 mg / ml Suspension to be nebulized -20 single-dose containers of 2 ml AIC n. 036922019
BUDEXAN 0.5 mg / ml Suspension to be nebulised -20 single-dose containers of 2 ml AIC n. 036922021
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
January 2008
