Active ingredients: Budesonide
Pulmaxan 0.125 mg / ml suspension for nebuliser
Pulmaxan 0.25 mg / ml suspension for nebuliser
Pulmaxan 0.5 mg / ml suspension for nebuliser
Pulmaxan package inserts are available for pack sizes: - Pulmaxan 0.125 mg / ml suspension for nebuliser, Pulmaxan 0.25 mg / ml suspension for nebuliser, Pulmaxan 0.5 mg / ml suspension for nebuliser
- Pulmaxan 100 micrograms / part, inhalation powder, Pulmaxan 200 micrograms / part, inhalation powder, Pulmaxan 400 micrograms / part, inhalation powder
Indications Why is Pulmaxan used? What is it for?
Pulmaxan is a nebulised inhalation medicine that contains the active substance budesonide.
Budesonide belongs to a group of medicines called 'glucocorticoids' which work by reducing and preventing swelling and inflammation of the lungs by helping air to pass through.
Pulmaxan is indicated in adults and children aged 6 months and over in the treatment of:
- asthma (an "inflammation of the airways, which makes it difficult to breathe), even for those who are unable to use spray inhalers or dry powder inhalers properly
- subglottic laryngitis or pseudocroup (disease characterized by swelling of the tissues under the vocal cords that makes it difficult to breathe) when it is very severe and hospitalization is indicated.
Contraindications When Pulmaxan should not be used
Do not take Pulmaxan
- if you are allergic to budesonide or any of the other ingredients of this medicine (listed in section 6).
Precautions for use What you need to know before taking Pulmaxan
Talk to your doctor or pharmacist before taking Pulmaxan:
- if you have problems with your adrenal glands (glands above the kidneys that can produce different types of hormones)
- if you have undergone treatment with high doses of glucocorticoids (anti-inflammatory) or prolonged treatment with high doses of inhalational glucocorticoids
- if you are in a period of severe physical stress such as in the case of surgery.
- if you have liver problems
- if you are taking ketoconazole and itraconazole (medicines used to treat fungal infections) (see also section "Other medicines and Pulmaxan")
- if you are taking medicines used to treat HIV infection
- if you have lung infections (such as pulmonary tuberculosis) or respiratory tract infections
- if you have infections including fungal or viral infections (measles and chickenpox)
- if you have glaucoma (eye disease caused by an increase in the pressure of the fluid inside the eye)
- if you suffer from cataracts (opacification of the lens, the lens of the eye that is used to focus images).
Pulmaxan is not suitable for the rapid improvement of sudden asthma attacks, for which a short-acting bronchodilator must be used. Your doctor will carefully evaluate the most suitable therapy for you.
Switching from systemic (i.e. taken orally, intramuscularly, or intravenously) glucocorticoid (anti-inflammatory) therapy to inhaled glucocorticoid therapy
If you switch from treatment with systemic (e.g. oral) glucocorticoids (anti-inflammatory) to treatment with inhaled glucocorticoids, your doctor will gradually reduce the dose of the systemic glucocorticoid you are taking. In this phase, you may experience general malaise such as muscle and / or joint pain. In rare cases, symptoms such as tiredness, depression, headache (headache), nausea and vomiting may appear.
You may experience these symptoms despite maintaining or even improving your lung function. If you experience these symptoms, your doctor will have you continue your Pulmaxan therapy, and will ask you to have blood tests to evaluate the function of your adrenal glands (glands on top of the kidneys that can produce different types of hormones). Depending on how well your adrenal glands are functioning, your doctor may temporarily increase the dose of the systemic glucocorticoid you are taking, and the switch to Pulmaxan may continue later, more slowly.
If you are under physical stress during this transition phase (for example in case of severe infections, trauma or surgery) or have a severe asthma attack, your doctor may prescribe additional treatment with systemic glucocorticoids (for example systemically ).
Additionally, switching from systemic glucocorticoid treatment to inhalation therapy can lead to allergies, such as rhinitis and eczema (irritation and inflammation of the nose or skin), which were previously controlled by systemically administered drug. If this happens, consult your doctor who will prescribe the appropriate therapy to control these symptoms.
Oral candidiasis (thrush, a mouth infection)Oral candidiasis may occur during therapy with inhaled glucocorticoids.
If this happens, please contact your doctor. Your doctor will prescribe the appropriate therapy for you and stop treatment if necessary (see also section 3 "How to take Pulmaxan").
Possible side effects of inhalational (anti-inflammatory) glucocorticoids when used in high doses for prolonged periods
Inhaled glucocorticoids can cause side effects. In particular, if used at high doses for prolonged periods, the following side effects may occur: Cushing's syndrome and Cushingoid appearance (disease characterized by an excessive production of a glucocorticoid hormone, cortisol, which manifests itself with a full moon, increased body weight, fluid retention, reduced sugar tolerance and increased risk of diabetes, leg swelling, headache, etc.), adrenal suppression (severe impairment of adrenal gland activity), decreased bone mass, cataract (clouding of the lens, the lens of the eye used to focus images), glaucoma (eye disease caused by an increase in the pressure of the fluid contained within the eye). These effects are less likely to occur than in treatment with glucocorticoids taken orally.
Rarely, a range of psychological and behavioral effects may occur, including psychomotor hyperactivity (behavioral disorder manifested by excessive motor activity), sleep disturbances, anxiety, depression, aggression, behavioral disturbances.
Therefore based on the above it is important that you take your dose as indicated in the package leaflet or as prescribed by your doctor. Therefore, you should not increase or decrease the dose without first consulting your doctor (see section 3 "How to take Pulmaxan").
Paradoxical bronchospasm
As with other therapies administered by inhalation, paradoxical bronchospasm (unexpected narrowing of the bronchial tubes causing severe breathing difficulties due to a reduced passage of air) may occur after administration with an immediate increase in wheezing (accompanied breathing difficulty). wheezing, i.e. whistling) In this case, you should consult your doctor immediately, who may, if necessary, stop treatment with budesonide for inhalation.The doctor will consider starting alternative therapy if necessary.
For those who carry out sporting activities
The use of the drug without therapeutic necessity constitutes doping and can in any case determine positive anti-doping tests.
Children and adolescents
Pulmaxan should be used with caution in children.
Influence on growth
The use of inhaled glucocorticoids may affect the growth of children and adolescents (see section "Additional side effects in children and adolescents"). Therefore, it is recommended that the height of children on prolonged treatment with inhaled glucocorticoids is periodically checked by the doctor. If growth is slowed, the doctor will re-evaluate therapy to reduce the dose of inhaled glucocorticoids. Your doctor will carefully evaluate the benefits of glucocorticoid therapy and the possible risk of growth block. If necessary, your doctor will advise you to go to a pediatric pulmonologist (pediatrician who specializes in treating diseases of the respiratory tract).
Also, in rare cases, prolonged treatment with inhaled glucocorticoids can cause behavioral disturbances in children.
Interactions Which drugs or foods may change the effect of Pulmaxan
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 drug used in the treatment of asthma. In particular, tell your doctor or pharmacist if you are taking:
- ketoconazole and itraconazole (medicines used to treat fungal infections) (see section "Warnings and precautions")
- medicines that contain hormones (estrogen) or oral contraceptives (pill)
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 using this medicine.
- The studies carried out do not indicate any undesirable effects on the health of the fetus / newborn with the use of budesonide for inhalations during pregnancy. As with other medicines, consult your doctor for the administration of budesonide during pregnancy, as it is necessary that the The physician evaluates the expected benefits to the mother versus the risks to the fetus
- Budesonide passes into breast milk. However, no effects on the suckling child are expected at the recommended doses of Pulmaxan. Budesonide can be used during breastfeeding.
Driving and using machines
Pulmaxan does not affect the ability to drive and use machines
Dosage and method of use How to use Pulmaxan: Dosage
Always take this medicine exactly as your doctor or pharmacist has told you. If in doubt, consult your doctor or pharmacist.
ASTHMA
INITIAL DOSE
Pulmaxan dosage is individual.
Adults and the elderly
The recommended starting dose is 0.5-1 mg twice a day. If necessary, your doctor may increase the dose of Pulmaxan (see dosing table).
MAINTENANCE DOSE
The maintenance dose is individual. Once control of asthma has been achieved, the maintenance dose should be the minimum dose that allows effective control of symptoms: your doctor will gradually reduce the medicine until the minimum dose is reached.
DOSAGE TABLE
* The product must be mixed with 0.9% physiological solution (saline solution) until reaching the volume of 2 ml.
ONSET OF THE EFFECT
Improvement in asthma control following administration of Pulmaxan may occur within 3 days of starting treatment, although maximum benefit is obtained after 2-4 weeks.
Patients treated with oral (anti-inflammatory) glucocorticoids
With the use of Pulmaxan it is possible to replace or significantly reduce the dose of glucocorticoids taken orally, while maintaining control of asthma. The transition from oral glucocorticoid therapy to Pulmaxan therapy will be evaluated by your doctor based on your general condition.
For about 10 days your doctor will prescribe a high dose of Pulmaxan to be taken in combination with the oral medicine you are already taking.
After that, your doctor will gradually reduce the dose of the oral medicine to the lowest possible level. In many cases, it is possible to completely replace oral therapy with Pulmaxan. For more information, see section "Warnings and precautions".
DIVISION OF THE DOSE AND MIXING
Pulmaxan can be mixed with 0.9% physiological solution (saline) and nebulised solutions of terbutaline, salbutamol, fenoterol, acetylcysteine, sodium cromoglycate or ipratroprium (medicines used to treat respiratory tract disorders).
The mixture should be used within 30 minutes.
In case a dose adjustment of Pulmaxan is required, the contents of the single-dose vial can be divided.
In fact, a line is clearly visible on the 2 ml containers of Pulmaxan 0.25 mg / ml suspension for nebuliser and Pulmaxan 0.5 mg / ml suspension for nebuliser. When the single-dose vial is held upside down, the line indicates a volume of 1 ml.
If you only use 1 ml, you must pour the contents of the single-dose vial until the surface of the liquid reaches the indicated line.
The opened single-dose container, still containing part of the liquid, must be kept in the bag, away from light and must be used within 12 hours.
Before using the remaining liquid, shake the contents carefully with a twisting motion. Once the foil pouch has been opened, the still closed containers are valid for 3 months and must be kept in the pouch protected from light.
Use in children and adolescents
ASTHMA
Children from 6 months of life
- Pulmaxan dosage is individual. The recommended starting dose is 0.25-0.5 mg per day. If the need arises, your doctor may increase the dose of Pulmaxan.
SUBGLOTTIGAL LARYNGITIS OR PSEUDOCROUP (for severe forms for which hospitalization is indicated)
Babies and children
- the usual recommended dose is 2 mg of Pulmaxan which can be given as a single dose or as two 1 mg doses 30 minutes apart. Dosage can be repeated every 12 hours for up to 36 hours or for as long as your doctor has prescribed you. Pulmaxan should be used with caution in children (see section "Children and adolescents").
INSTRUCTIONS FOR THE CORRECT USE OF PULMAXAN
Pulmaxan must be used with a jet nebulizer. The vapors produced by the nebulizer are inhaled from the mouth through a mouthpiece or suitable face mask. The nebulizer must consist of: a compressor (a pump) capable of generating an adequate air flow (5-8 L / min) and an ampoule (a tank), in which the medicine solution is placed, having a volume of 2-4 ml. Ultrasonic nebulizers are not suitable for the administration of Pulmaxan.
INSTRUCTIONS FOR USE
- Gently shake the single-dose container with a twisting motion.
- Hold the single-dose container upright (see figure) and open by rotating the flap until the single-dose vial opens.
- Put the open end of the single-dose container well into the nebulizer tank and squeeze slowly.
- Before turning on the nebulizer, carefully read the instructions for use given in the package leaflet found in the package of each nebulizer. If you are unsure about the use of the nebulizer, ask your doctor or pharmacist.
NOTE:
- After inhalation, you should rinse your mouth with water to minimize the risk of developing oropharyngeal candida infections (thrush, mouth and throat infection).
- If you are using a face mask to inhale the vapor, you need to make sure that the mask adheres well when spraying. After using the face mask, you should wash your face with water to prevent irritation.
- Clean and maintain the nebulizer according to the manufacturer's instructions.
CLEANING THE NEBULIZER
The nebulizer reservoir 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.
Overdose What to do if you have taken too much Pulmaxan
If you take more Pulmaxan than you should
Accidental intake of an overdose of Pulmaxan should not cause any discomfort. In case of accidental intake of an overdose of Pulmaxan notify your doctor immediately or contact the nearest hospital.
If you forget to take Pulmaxan
Do not take a double dose to make up for a forgotten dose.
If you stop using Pulmaxan
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
Side Effects What are the side effects of Pulmaxan
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Undesirable effects are listed below according to the following frequency:
Common (may affect up to 1 in 10 patients)
- candida infections in the oropharynx (thrush, infection of the mouth and throat and mouth)
- nausea
- cough, hoarseness (when the voice is shrill or low), throat irritation
Rare (may affect up to 1 in 10,000 patients)
- immediate or delayed allergic reactions * including rash (skin rash), contact dermatitis (inflammation of the skin usually manifested by redness, blisters, blisters, abrasions and scabs), hives (redness of the skin accompanied by itching), angioedema ( swelling) and anaphylactic reaction (severe allergic reaction)
- signs and symptoms of systemic (i.e. taken by mouth, intramuscular, or intravenous route) glucocorticoid effects, including adrenal suppression (severe impairment of adrenal gland activity)
- restlessness, nervousness, depression, behavioral changes, sleep disturbances, anxiety, psychomotor hyperactivity (behavioral disorder manifested by excessive motor activity), aggression
- bronchospasm (narrowing of the bronchi which causes difficulty in breathing due to a reduced passage of air)
- bruising (bruising), skin striae (striae on the skin similar to stretch marks, reddish-purple in color)
* Facial skin irritation, as an example of an allergic reaction, has appeared in some cases where a nebulizer with mask has been used. To prevent irritation, the facial skin should wash the face with water after using the facial mask.
Not known (frequency cannot be estimated from the available data)
- glaucoma (eye disease caused by an increase in the pressure of the fluid contained within the eye), cataract (clouding of the lens, the lens of the eye used to focus images)
Additional side effects in children and adolescents
Undesirable effects are listed below according to the following frequency:
Rare (may affect up to 1 in 10,000 patients)
- slowdown in growth
- dysphonia (difficulty producing the voice), hoarseness (when the voice is shrill or low)
- behavioral disturbances.
Given the risk of growth retardation in the pediatric patient population, growth should be monitored as described in the section "Children and adolescents".
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 https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects you can help provide more information on safety. of this medicine.
Expiry and Retention
- 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 EXP.
- Do not store above 30 ° C. The product must be stored in an upright position.
- Keep the containers in the foil pouch to protect the medicine from light. Do not freeze.
- After opening the foil pouch, the unopened containers must be kept in the pouch, protected from light and used within 3 months. Once opened, the single-dose container must be used within 12 hours.
- 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.
Composition and pharmaceutical form
Contents of the pack and other information
Pulmaxan 0.125 mg / ml suspension for nebuliser
- the active ingredient is: budesonide (each 2 ml single-dose container contains 0.25 mg of budesonide).
- the other ingredients are: disodium edetate, sodium chloride, polysorbate 80, anhydrous citric acid, sodium citrate, water for injections.
Pulmaxan 0.25 mg / ml suspension for nebuliser
- the active ingredient is: budesonide (each 2 ml 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.
Pulmaxan 0.5 mg / ml suspension for nebuliser
- the active ingredient is: budesonide (each 2 ml 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 Pulmaxan looks like and contents of the pack
Pulmaxan is presented as a white or almost white suspension to be nebulised.
Each pack:
Pulmaxan 0.125 mg / ml suspension for nebuliser,
Pulmaxan 0.25 mg / ml suspension for nebuliser
Pulmaxan 0.5 mg / ml suspension for nebuliser contains 4 aluminum sachets.
Each foil pouch contains 5 containers.
Each single-dose container contains 2 ml of suspension to be nebulised.
Overall, each Pulmaxan package contains 20 containers.
A line is clearly visible on each single-dose container of Pulmaxan 0.25 mg / ml suspension for nebuliser and Pulmaxan 0.5 mg / ml suspension for nebuliser. When the single-dose container is held upside down, the line indicates a volume of 1 ml.
Not all pack sizes may be marketed.
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
PULMAXAN SUSPENSION FOR NEBULIZER
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Pulmaxan 0.125 mg / ml suspension for nebuliser
1 single-dose container contains:
active ingredient: budesonide 0.25 mg.
Pulmaxan 0.25 mg / ml suspension for nebuliser
1 single-dose container contains:
active ingredient: budesonide 0.5 mg.
Pulmaxan 0.5 mg / ml suspension for nebuliser
1 single-dose container contains:
active ingredient: budesonide 1 mg.
For the full list of excipients, see 6.1.
03.0 PHARMACEUTICAL FORM
Suspension for nebulizer.
White to off-white suspension.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Pulmaxan Nebuliser Suspension is indicated for the treatment of bronchial asthma including in patients who are unable to use properly spray or dry powder inhalers.
Pulmaxan Nebuliser Suspension is also indicated for 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 Pulmaxan suspension for nebuliser is individual.
Recommended starting dose:
CHILDREN 6 months or older: 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 ELDERLY: 0.5-1 mg twice daily. If necessary, the dose can be further increased.
In cases where a greater therapeutic effect is required, higher doses of Pulmaxan suspension for nebulizer can be administered; in fact the risks of systemic effects are low, if compared with those detectable following a treatment in combination with oral steroids.
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 THE EFFECT
Improvement in asthma control following administration of Pulmaxan inhaled 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)
Pulmaxan 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 Pulmaxan, the patient should be in a relatively stable phase. A high dose of Pulmaxan 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 (for example by 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 Pulmaxan. For more information on corticosteroid withdrawal, see section 4.4.
DIVISION OF THE DOSE AND MIXING
Pulmaxan suspension for nebuliser can be mixed with 0.9% saline and nebulisation solutions of terbutaline, salbutamol, fenoterol, acetylcysteine, sodium cromoglycate or ipratroprium.
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 Pulmaxan 0.25 mg / ml suspension for nebuliser and Pulmaxan 0.5 mg / ml suspension for nebuliser. 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.
Keep the single-dose container open in the bag, away from light.
The single-dose container, when opened, must be used within 12 hours.
Before using the remaining liquid, shake the contents carefully with a twisting motion.
Once the foil pouch has been opened, the single-dose containers are valid for 3 months and must be kept in the pouch protected from light.
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 Pulmaxan suspension for nebuliser which can be given as a single dose or as two 1 mg doses 30 minutes apart. The dosage can be repeated. every 12 hours for up to 36 hours or until clinical improvement.
INSTRUCTIONS FOR THE CORRECT USE OF PULMAXAN SUSPENSION FOR NEBULIZER
Pulmaxan suspension for nebulizer must be administered with a jet nebulizer equipped with a mouthpiece or suitable face mask. The nebulizer must be connected to a compressor with adequate flow (5-8 l / min) and a filling volume of 2-4 ml. Ultrasonic nebulisers are not suitable for the administration of Pulmaxan Nebuliser Suspension.
Instructions for Use
1) Gently shake the single-dose container with a rotating motion.
2) Hold the single-dose container in vertical position and open by rotating the flap until the container opens.
3) Put the open end of the single-dose container well into the nebulizer tank and press slowly.
NOTE:
1) The patient should rinse his mouth with water after inhalation in order to minimize the risk of oropharyngeal candida infections.
2) It is important to inform the patient / caregiver to wash their face with water after using the mask to prevent irritation of the facial skin.
3) 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.
4) Carefully read the instructions for use contained in the package leaflet found in the package of each nebulizer.
5) Clean and maintain the nebulizer according to the manufacturer's instructions.
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.
04.3 Contraindications
Hypersensitivity to budesonide or to any of the excipients.
04.4 Special warnings and appropriate precautions for use
Pulmaxan 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 doses 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. A 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 the maintenance or even improvement of lung function during the period of withdrawal of oral steroid treatment. Such patients should be encouraged to continue therapy with Pulmaxan 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 Pulmaxan 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 require 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 rate of elimination and higher systemic exposure. This may be clinically relevant in patients with severely impaired liver function.
You need 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 4.5).
Particular 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.
Pulmaxan 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).
In long-term treatment with high doses of Pulmaxan, local and systemic effects may occur in humans. Systemic effects with inhaled corticosteroids occur less frequently than with oral corticosteroids.
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 is the lowest possible dose with which effective control of asthma is maintained. Therefore, on the basis of the above, once asthma control is achieved, the dose to be used in maintenance treatment should be the least effective.
Pulmaxan should be used with caution in children.
As with other inhaled therapies, paradoxical bronchospasm may arise with an immediate increase in wheezing after administration. In this case, 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).
As no data is available to support a dosage recommendation, the combination of these drugs should be avoided. If this is not possible, the longest possible time should elapse between the two treatments and a reduction in the dose of budesonide may 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).
Increased 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 the function of the adrenal glands can be inhibited, an ACTH stimulation test to diagnose "pituitary insufficiency may give false results (low values)."
At recommended doses, cimetidine has a slight effect on the pharmacokinetics of orally administered budesonide which is not clinically relevant.
04.6 Pregnancy and lactation
The results emerged from large prospective epidemiological studies and from experience post-marketing on a worldwide scale, they 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 Pulmaxan. Budesonide can be used during breastfeeding.
Maintenance therapy with inhaled budesonide (200 or 400 micrograms twice daily) in lactating 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
Pulmaxan 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.
The following definitions refer to the incidence of undesirable effects.
Frequencies are defined as: very common (≥ 1/10), common (≥1 / 100 to> 1,000 a
* Refer to Description of selected Adverse Reactions; facial skin irritation, listed below.
** Please 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.
Ask the patient to report any symptoms or signs not described above to the doctor or pharmacist.
04.9 Overdose
Acute overdose with Pulmaxan Nebuliser Suspension, even in high doses, should not cause clinical problems.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: other anti-asthma, inhalers, glucocorticoids.
ATC code: R03BA02.
Budesonide is a glucocorticosteroid with high local anti-inflammatory activity.
Topical 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 asthma 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 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 Pulmaxan in healthy volunteers have shown dose-related effects on plasma and urinary cortisol. The ACTH test has shown that treatment with Pulmaxan, at recommended dosages, produces significantly less effects on adrenal function than prednisone 10 mg.
Pediatric population
Clinic - asthma
The efficacy of Pulmaxan has been evaluated in a large number of studies, and Pulmaxan has been shown to be effective in both adults and children, as a prophylactic treatment of persistent asthma once or twice a day. Some examples of representative studies are shown. below.
Clinic - laryngotracheobronchitis
A series of studies in children with laryngotracheobronchitis compared Pulmaxan with placebo. Examples of representative studies evaluating the use of Pulmaxan 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 in 87 children (7 months to 9 years), hospitalized with a clinical diagnosis of laryngotracheobronchitis, was conducted to determine whether Pulmaxan improves laryngotracheobronchitis symptom score or shortens duration. of hospital stay. An initial dose of Pulmaxan (2 mg) or placebo was followed by Pulmaxan 1 mg or placebo every 12 hours. Pulmaxan statistically significantly improved the 12- and 24-hour and 2-hour laryngotracheobronchitis scores 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 Pulmaxan 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 Pulmaxan 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 Pulmaxan 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 Pulmaxan 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 following administration of Pulmaxan Nebuliser Suspension via a jet nebuliser is approximately 15% of the nominal dose and 40-70% of the delivered dose 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 from the start of nebulization, is approximately 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 low glucocorticosteroid activity. The main metabolites are 6b-hydroxybudesonide and 16a-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. In asthmatic children, aged 4-6 years, the systemic bioavailability of budesonide following administration of Pulmaxan suspension for nebulizer through a jet nebulizer (PARI LC Plus with Jet Pari Master compressor) is equal to approximately 6% of the nominal dose and 26% of the dose delivered to patients. In children, the systemic bioavailability is approximately half of 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 4-6 year old asthmatic children, the systemic clearance of budesonide is approximately 0.5 l / min. With reference to body weight, expressed in kg, children have a clearance that is approximately 50% higher than that found in adults. In asthmatic children, the terminal half-life of budesonide after inhalation is approximately 2.3 hours. This value is similar to that observed in healthy adults.
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, lymphoid and adrenal tissue atrophy .
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 4.2.
06.3 Period of validity
2 years.
06.4 Special precautions for storage
The product must be stored in an upright position at a temperature not exceeding 30 ° C and the single-dose containers must be kept in the aluminum bag protected from light. Do not freeze.
After opening the foil pouch, the single-dose containers must be used within 3 months.
The opened single-dose container must be used within 12 hours.
After opening the foil pouch, unused single-dose containers must be kept in the pouch, protected from light.
06.5 Nature of the immediate packaging and contents of the package
Primary container: single-dose container of LD-polyethylene. Each unit contains 2 ml of suspension. A line is clearly visible on each single-dose container of Pulmaxan 0.25 mg / ml suspension for nebuliser and Pulmaxan 0.5 mg / ml suspension for nebuliser. When the single-dose container is held upside down, the line indicates a volume of 1 ml. Packs of 5 units wrapped in a sealed foil pouch.
Pack of 20 single-dose containers of 2 ml.
06.6 Instructions for use and handling
See 4.2
07.0 MARKETING AUTHORIZATION HOLDER
AstraZeneca S.p.A.
Volta Palace
Via F. Sforza
Basiglio (MI)
08.0 MARKETING AUTHORIZATION NUMBER
Pulmaxan 0.125 mg / ml suspension for nebulizer - A.I.C. n. 027621046 - NON-COMMERCE PACKAGING
Pulmaxan 0.25 mg / ml suspension for nebulizer - A.I.C. n. 027621059
Pulmaxan 0.5 mg / ml suspension for nebulizer - A.I.C. n. 027621061
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
AIC date: 25.11.2000
Renewal date: 30.12.2008
10.0 DATE OF REVISION OF THE TEXT
June 2015