Active ingredients: Budesonide, Formoterol (formoterol fumarate dihydrate)
Symbicort Turbohaler 160 micrograms / 4.5 micrograms / inhalation, inhalation powder
Symbicort package inserts are available for pack sizes:- Symbicort Turbohaler 160 micrograms / 4.5 micrograms / inhalation, inhalation powder
- Symbicort Turbohaler 320 micrograms / 9 micrograms, inhalation powder
Why is Symbicort used? What is it for?
Symbicort Turbohaler is an inhaler used to treat asthma in adults and adolescents between the ages of 12 and 17. It is also used to treat the symptoms of chronic obstructive pulmonary disease (COPD) in adults aged 12 to 17 years. 18. Contains two different medicines: budesonide and formoterol fumarate dihydrate.
- Budesonide belongs to a group of medicines called 'corticosteroids'. It works by reducing and preventing swelling and inflammation in your lungs.
- Formoterol fumarate dihydrate belongs to a group of medicines called "β2 - long-acting" adrenoceptor agonists "or" bronchodilators. "It works by relaxing the muscles in the airways, making it easier to breathe.
Asthma
Symbicort Turbohaler can be prescribed for asthma in two different ways.
a) Some people are prescribed two inhalers for asthma: Symbicort Turbohaler and a separate "reliever inhaler".
- They use Symbicort Turbohaler every day. This helps prevent asthma symptoms from appearing.
- They use the "as-needed inhaler" when asthma symptoms appear, to facilitate breathing again.
b) Some people are prescribed Symbicort Turbohaler as their only inhaler for asthma.
- They use Symbicort Turbohaler every day. This helps prevent asthma symptoms from appearing.
- They still use Symbicort Turbohaler when they need extra doses for the relief of asthma symptoms, to make breathing easier. They do not need a separate inhaler for this purpose.
Chronic Obstructive Pulmonary Disease (COPD)
Symbicort Turbohaler can also be used to treat the symptoms of severe COPD in adults. COPD is a chronic disease of the lung airways, often caused by cigarette smoking.
What Symbicort Turbohaler contains
The active ingredients are budesonide and formoterol fumarate dihydrate. Each inhaled dose contains 160 micrograms of budesonide and 4.5 micrograms of formoterol fumarate dihydrate.
The other ingredient is lactose monohydrate (which contains milk proteins).
Contraindications When Symbicort should not be used
The use of Symbicort Turbohaler is contraindicated in case of persensitivity (allergy) to budesonide, formoterol or lactose.
Precautions for use What you need to know before taking Symbicort
Do not use Symbicort Turbohaler
If you are allergic to budesonide, formoterol or any of the other ingredients of this medicine (listed in section 6), i.e. lactose (which contains small amounts of milk protein).
Warnings and Precautions
Talk to your doctor or pharmacist before using Symbicort Turbohaler if:
- He is diabetic.
- He has a "lung infection.
- Have high blood pressure or have ever had heart problems in the past (e.g. irregular heartbeat, very fast pulse, narrowing of the arteries or heart failure).
- You have problems with your thyroid or adrenal glands.
- You have low blood potassium levels.
- You have severe liver problems
Interactions Which drugs or foods may change the effect of Symbicort
Other medicines and Symbicort Turbohaler
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines
In particular, tell your doctor or pharmacist if you are taking any of the following medicines:
- Beta blockers (such as atenolol or propranolol for hypertension), including eye drops (such as timolol for glaucoma).
- Medicines for fast or irregular heartbeat (such as quinidine).
- Medicines such as digoxin, often used to treat heart failure.
- Diuretics (such as furosemide), used to treat hypertension.
- Steroids taken by mouth (such as prednisolone).
- Xanthines (such as theophylline or aminophylline), often used to treat asthma.
- Other bronchodilators (such as salbutamol).
- Tricyclic antidepressants (such as amitriptyline) and the antidepressant nefazodone.
- Phenothiazine medicines (such as chlorpromazine and prochlorperazine).
- Medicines called "HIV protease inhibitors" (such as ritonavir) used to treat HIV infection.
- Medicines to treat infections (such as ketoconazole, itraconazole, voriconazole, posaconazole, clarithromycin and telithromycin). Medicines for Parkinson's disease (such as levodopa).
- Medicines for thyroid problems (such as levothyroxine).
If any of the above apply to you, or if you are in any doubt, consult your doctor or pharmacist before using Symbicort Turbohaler.
Also tell your doctor or pharmacist if you need to undergo "general anesthesia for surgery or dental work."
Warnings It is important to know that:
Pregnancy and breastfeeding
- If you are pregnant, or planning to become pregnant, consult your doctor before taking Symbicort Turbohaler - do not take Symbicort Turbohaler unless directed by your doctor.
- If you become pregnant while taking Symbicort Turbohaler, do not stop using Symbicort Turbohaler but consult your doctor immediately.
- If you are breastfeeding, tell your doctor before taking Symbicort Turbohaler.
Driving and using machines
Symbicort Turbohaler has no or negligible effect on the ability to drive or use tools or machines.
Symbicort Turbohaler contains lactose
Symbicort Turbohaler contains lactose, which is a type of sugar. If your doctor has told you that you have an "intolerance to some sugars, consult your doctor before using this medicine. The amount of lactose contained in this medicine does not normally cause problems in lactose intolerant people.
The lactose excipient contains small amounts of milk proteins which can cause allergic reactions.
Dose, Method and Time of Administration How to use Symbicort: Posology
- Always use this medicine exactly as your doctor has told you. Consult your doctor or pharmacist if you have any questions.
- It is important to use Symbicort Turbohaler every day, even if you have no asthma or COPD symptoms at the moment.
- If you are using Symbicort Turbohaler for asthma, your doctor will want to check your symptoms periodically.
If you have taken steroid tablets for your asthma or COPD, your doctor may reduce the number of tablets you are taking once you start using Symbicort Turbohaler. If you have been taking steroid tablets for a long time, your doctor may ask you to have blood tests periodically. When you reduce the amount of oral steroids you may feel generally unwell although your respiratory symptoms may be improved. You may experience symptoms such as nasal congestion and runny nose (runny nose), muscle or joint weakness or pain, and rash (eczema). If any of these symptoms worry you or if you experience symptoms such as headache, tiredness, nausea or vomiting please contact your doctor immediately. You may need to take another medicine if you have allergic or arthritic symptoms. Ask your doctor if you are unsure whether or not to continue Symbicort Turbohaler therapy.
Your doctor may consider adding steroid tablets to your usual treatment during times of stress (for example when you have a respiratory infection or before surgery).
Important information about asthma or COPD symptoms
If you notice wheezing or wheezing while using Symbicort Turbohaler you should continue to use it but consult your doctor as soon as possible as additional treatment may be required.
Contact your doctor immediately if:
- Breathing gets worse or wakes up frequently at night due to asthma.
- If you start to feel tightness in your chest in the morning or if the tightness in your chest lasts longer than usual.
These signs could mean that your asthma or COPD is not properly controlled and that you may need different or additional treatment right away.
Asthma
Symbicort Turbohaler can be prescribed for asthma in two different ways. The amount of Symbicort Turbohaler to use and when to use it depends on your doctor's prescription.
a) If you have been prescribed Symbicort Turbohaler and a separate reliever inhaler, please read the section "a) Using Symbicort Turbohaler and a separate reliever inhaler".
b) If you have been prescribed Symbicort Turbohaler as your only inhaler, please read section "b) Using Symbicort Turbohaler as your only inhaler for" asthma ".
a) Using Symbicort Turbohaler and a separate inhaler for use as needed Use Symbicort Turbohaler every day. This helps prevent asthma symptoms from appearing.
Adults (18 years of age and older)
- The usual dose is 1 or 2 inhalations, twice a day.
- Your doctor may increase this dose to 4 inhalations, twice a day.
- If your symptoms are well controlled, your doctor may ask you to take the medicine once a day
Teenagers (12-17 years)
- The usual dose is 1 or 2 inhalations, twice a day.
- If your symptoms are well controlled your doctor may ask you to take the medicine once a day
A lower dosage of Symbicort Turbohaler is available for children 6 to 11 years of age.
Symbicort Turbohaler is not recommended for children under 6 years of age.
Your doctor (or nurse) will help you manage your asthma and adjust the dose of this medicine to the lowest one that controls asthma. However, do not change the dose without talking to your doctor (or nurse) first.
Use the separate "reliever inhaler" to treat asthma symptoms when they appear.
Always keep your "reliever inhaler" with you, to use when you need it. Do not use Symbicort Turbohaler to treat asthma symptoms, but the reliever inhaler.
b) Use of Symbicort Turbohaler as the only inhaler for asthma
Only use Symbicort Turbohaler in this way as directed by your doctor and if you are over 18 years of age.
Use Symbicort Turbohaler every day. This helps prevent asthma symptoms from appearing. It can assume:
- 1 inhalation in the morning and 1 inhalation in the evening.
or
- 2 inhalations in the morning
or
- 2 inhalations in the evening.
Your doctor may increase this dose to 2 inhalations, twice a day.
Also use Symbicort Turbohaler as a 'reliever inhaler' to treat asthma symptoms when they appear
- If asthma symptoms appear, take 1 inhalation and wait a few minutes.
- If you don't feel better, take another inhalation.
- Do not take more than 6 inhalations at one time.
Always keep Symbicort Turbohaler with you, to use it when needed.
A total daily dose greater than 8 inhalations is not normally required. However, your doctor may allow you to take up to 12 inhalations per day for a limited time.
If you need to use 8 or more inhalations a day regularly, consult your doctor or nurse as your treatment may need to be adjusted.
Do not use more than 12 inhalations in total in 24 hours.
If you experience asthma symptoms while exercising, use Symbicort Turbohaler as described in this leaflet. However, do not use Symbicort Turbohaler just before exercise to prevent symptoms from appearing.
Chronic Obstructive Pulmonary Disease (COPD)
- Use is intended for adults only (18 years of age and older).
- The usual dose is 2 inhalations twice a day.
Your doctor may also prescribe other bronchodilator medicines, for example anticholinergics (such as tiotropium bromide or ipratropium bromide) to treat COPD.
How to prepare Symbicort Turbohaler
Before using a new Symbicort Turbohaler for the first time, it must be prepared for use as follows:
- Unscrew and remove the cap; a noise may be heard.
- Hold the Symbicort Turbohaler upright with the red wheel facing down.
- Turn the red wheel in one direction as far as it will go. Then turn in the other direction again as far as it will go (it does not matter in which direction you start turning the wheel). During this operation you will hear a click.
- Repeat the operation, turning the red wheel in both directions.
- Symbicort Turbohaler is now ready for use.
How to take an "inhalation
Whenever you need to take an inhalation, follow the instructions below.
- Unscrew and remove the cap; a noise may be heard.
- . Hold the Symbicort Turbohaler upright with the red wheel facing down
- Do not touch the mouthpiece when charging Symbicort Turbohaler. To load Symbicort Turbohaler with one dose, turn the red wheel in one direction as far as it will go.
Then turn in the other direction as far as it will go (it does not matter in which direction you start turning the wheel). You will hear a click during this operation. Symbicort Turbohalere is now charged and ready for use. Only charge Symbicort Turbohaler when you need to use it. - Keep Symbicort Turbohaler away from your mouth. Breathe out gently (without forcing). Do not exhale through Symbicort Turbohaler.
- Place the mouthpiece gently between your teeth. Close your lips and inhale as deeply as possible through your mouth. Do not chew or bite the mouthpiece.
- Remove Symbicort Turbohaler from your mouth. Gently exhale. The amount of medicine inhaled is very small. This means that you may not taste it after inhalation. If you have followed the instructions, you can be sure that you have inhaled the dose and the medicine is now in your lungs.
- If a second inhalation is to be taken, repeat steps 2 to 6.
- After use, replace the cap and screw it back on.
- Rinse your mouth with water after your morning and / or evening dose and spit out the water.
Do not try to remove or twist the mouthpiece. It is attached to Symbicort Turbohaler and does not need to be removed. Do not use Symbicort Turbohaler if it is damaged or if the mouthpiece is detached from Symbicort Turbohaler
As with all inhalers, child caregivers must ensure that children who have been prescribed Symbicort Turbohaler use the correct inhalation technique, as described above.
How to clean Symbicort Turbohaler
Clean the outside of the mouthpiece once a week with a dry cloth. Do not use water or liquids.
When to start using a new inhaler
- The dose indicator tells you how many doses (inhalations) are left in the Symbicort Turbohaler, starting with 60 or 120 doses when full.
- The dose indicator reports 10-dose intervals, so it does not indicate every dose.
- When a red mark appears in the margin of the indicator window for the first time, it means that there are approximately 20 doses left. For the last 10 doses, the background of the dose indicator is red. When the "0" in the red background has reached the middle of the window, you need to start using a new Symbicort Turbohaler.
Note:
- It will still be possible to rotate the red wheel and hear the "click" even when Symbicort Turbohaler is empty.
- The sound you hear when you shake the Symbicort Turbohaler is produced by a drying agent and not by the medicine. Therefore, this sound does not indicate how much medicine is left in the Symbicort Turbohaler.
- If you accidentally charge Symbicort Turbohaler more than once before taking your dose, you will still only take one dose. However, the indicator will record all doses loaded.
If you forget to use Symbicort Turbohaler
- If you forget to take a dose, take it as soon as you remember it. However, if it is almost time for your next dose, skip the missed dose.
- Do not take a double dose to make up for a forgotten dose.
If you have any questions about the use of this product, ask your doctor or pharmacist.
Overdose What to do if you have taken an overdose of Symbicort
If you use more Symbicort Turbohaler than you should
If you use more Symbicort Turbohaler than you should contact your doctor or pharmacist.
You must not exceed the prescribed dose without consulting your doctor.
The most common symptoms that can occur if you use more Symbicort Turbohaler than you should are: tremor, headache or fast heart rate.
Side Effects What are the side effects of Symbicort
Like all medicines, this medicine can cause side effects, although not everybody gets them.
If any of the following occur, stop using Symbicort Turbohaler and contact your doctor immediately:
- Swelling of the face, particularly around the mouth (tongue and / or throat and / or difficulty in swallowing) or hives accompanied by difficulty in breathing (angioedema) and / or sudden fainting sensation. This could indicate an allergic reaction. This effect occurs rarely and affects less than 1 in 1,000 people.
- Suddenly wheezing and shorter breathing immediately after using the inhaler. If any of these occur, stop using Symbicort Turbohaler immediately and use your "as needed" inhaler. Contact your doctor immediately if you need to change your treatment. This rarely happens, affecting less than 1 in 10,000 people.
Other possible side effects:
Common (may affect 1 in 10 people)
- Palpitations (awareness of the heartbeat), tremor or agitation. If these effects occur, they are usually mild and disappear with continued Symbicort Turbohaler treatment.
- Thrush (a "fungal infection) in the mouth. This is less likely if you rinse your mouth with water after using Symbicort Turbohaler.
- Mild sore throat, cough and hoarseness.
- Headache.
Uncommon (may affect up to 1 in 100 people)
- Feeling restless, nervous or agitated.
- Disturbed sleep.
- Dizziness.
- Nausea (malaise).
- Rapid heartbeat.
- Skin bruising
- Muscle cramps.
Rare (may affect 1 in 1,000 people)
- Skin rash, itching.
- Bronchospasm (narrowing of the muscles in the airways, causing wheezing). If wheezing occurs soon after using Symbicort Turbohaler, stop using Symbicort Turbohaler and contact your doctor immediately.
- Low levels of potassium in the blood.
- Irregular heartbeat.
Very rare (may affect up to 1 in 10,000 people)
- Depression.
- Behavior changes, especially in children.
- Chest pain or tightness (angina pectoris).
- Increase in the amount of sugar (glucose) in the blood.
- Changes in taste, for example unpleasant taste in the mouth.
- Blood pressure changes
Inhaled corticosteroids can affect the normal production of steroid hormones in the body, particularly if high doses are used for a prolonged period. These effects include:
- Changes in bone mineral density (thinning of the bones).
- Cataract (clouding of the lens in the eye).
- Glaucoma (increased pressure in the eye).
- Slowing of growth in children and adolescents.
- Effect on the adrenal gland (a small gland near the kidney)
These effects are much less likely to occur with inhaled corticosteroids than with tablet corticosteroids.
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 on the website of the Italian Medicines Agency: www.agenziafarmaco.gov.it/it/responsabili.
By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
- Keep this Symbicort Turbohaler medicine out of the sight and reach of children.
- Do not use this medicine after the expiry date which is stated on the carton or on the label of your inhaler after EXP. The expiry date refers to the last day of the month.
- Do not store above 30 ° C.
- Keep the container / cap tightly closed to protect the medicine from moisture.
- Do not throw away 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.
What Symbicort Turbohaler looks like and contents of the pack
Symbicort Turbohaler consists of an inhaler that contains the medicine. The powder for inhalation is white in color. Each inhaler contains 60 doses and has a white body and a red wheel. The rotating bezel contains the Braille code with the number 6 for identification, to differentiate it from other AstraZeneca inhaler products.
Symbicort Turbohaler is available in packs containing 1, 2, 3, 10 or 18 inhalers containing 60 doses.
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
SYMBICORT 160 MCG / 4.5 MCG INHALATION, DUST FOR INHALATION
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each delivered dose (dose that comes out of the mouthpiece) contains: budesonide 160 mcg / inhalation and formoterol fumarate dihydrate 4.5 mcg / inhalation.
Each inhaled dose contains: budesonide 200 mcg / inhalation and formoterol fumarate dihydrate 6 mcg / inhalation.
Excipient: Lactose monohydrate 730 mcg contained in each dose.
For the full list of excipients see section 6.1.
03.0 PHARMACEUTICAL FORM
Powder for inhalation.
White powder.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Asthma
Symbicort is indicated in the regular treatment of asthma when the use of combination therapy (inhaled corticosteroid and long-acting β2-adrenoceptor agonist) is appropriate in:
- patients who are inadequately controlled on inhaled corticosteroids and "as needed" short-acting β2-agonist agonists.
or
- patients who are already adequately controlled on both inhaled corticosteroids and long-acting β2-agonist adrenoceptors.
COPD
Indicated in the symptomatic treatment of patients with severe chronic obstructive pulmonary disease (FEV1 significant symptoms despite regular therapy with long-acting bronchodilators.
04.2 Posology and method of administration
Route of administration: For inhalation use.
Asthma
Symbicort is not intended for the initial management of asthma. The dose of Symbicort components is individual and must be adjusted to the severity of the disease. This must be taken into consideration not only when initiating treatment with combination products but also when dosing If an individual patient requires a dosage other than that available in combination in the inhaler, appropriate doses of β2-adrenoceptor agonists and / or corticosteroids with separate inhalers should be prescribed.
The dose should be adjusted to the lowest level at which effective symptom control is maintained. Patients should be re-evaluated regularly by their doctor so that the dose of Symbicort remains optimal. When long-term symptom control is maintained with the lowest recommended dosage, the next step may be, as a trial, administration of inhaled corticosteroid alone.
For Symbicort there are two treatment modalities:
A. Symbicort maintenance therapy: Symbicort is taken as a regular maintenance treatment with another fast-acting bronchodilator for use as needed.
B. Symbicort maintenance and reliever therapy: Symbicort is taken as both regular maintenance and reliever treatment in response to symptoms.
A. Symbicort maintenance therapy
Patients should be advised to always have the other fast-acting bronchodilator available for emergency use.
Recommended doses:
Adults (aged 18 and over): 1-2 inhalations twice a day. Some patients may need up to 4 inhalations twice a day.
Teenagers (12-17 years): 1-2 inhalations twice a day.
In current practice, when symptom control is achieved with the twice daily dosing regimen, adjusting the dosage to the lowest therapeutically effective level could include administration of Symbicort once daily in the event that, in the opinion of the physician, the use of a long-acting bronchodilator in maintenance therapy is required.
Increasing use of other fast-acting bronchodilators indicates worsening of underlying conditions and necessitates a reassessment of asthma therapy.
Children (6 years and older): a lower dosage formulation is available for children 6 to 11 years of age.
Children under 6 years of age: as only limited data are available, Symbicort is not recommended in children below 6 years of age.
B. Symbicort maintenance and reliever therapy
Patients take a daily maintenance dose of Symbicort and also take Symbicort as needed in response to symptoms. Patients should be advised to always have Symbicort available for reliever use.
Symbicort maintenance and reliever therapy should be especially considered for patients with:
• inadequate asthma control and in the presence of frequent use of reliever medication;
• exacerbations of asthma that required medical intervention in the past.
Close monitoring for dose-related adverse events is required in patients who frequently take high numbers of Symbicort as-needed inhalations.
Recommended dosages:
Adults (aged 18 and over): The recommended maintenance dose is 2 inhalations per day, taken either as one inhalation in the morning and one in the evening or as 2 inhalations either in the morning or in the evening. For some patients a maintenance dose of 2 inhalations twice a day may be appropriate. Patients should take an additional inhalation as needed in response to symptoms. If symptoms persist after a few minutes, a further inhalation should be taken. No more than 6 inhalations should be taken on any single occasion.
A daily dose of more than 8 inhalations is not usually required; however, total daily doses of up to 12 inhalations can be taken for a limited period. Patients taking more than 8 inhalations per day should be strongly advised to seek medical advice. They must be re-evaluated and their maintenance therapy must be reconsidered.
Children and adolescents under the age of 18: Symbicort maintenance and reliever therapy is not recommended in children and adolescents.
COPD
Recommended doses:
Adults: 2 inhalations 2 times a day.
General informations
Special patient groups:
There are no special dosing requirements in elderly patients. There are no data available on the use of Symbicort in patients with hepatic or renal impairment. Since budesonide and formoterol are eliminated primarily by hepatic metabolism, increased drug exposure can be expected in patients with severe liver cirrhosis.
Instructions for the correct use of Symbicort:
The inhaler is driven by the inspiratory flow, which means that when a patient inhales through the mouthpiece, the substance enters the airways with the inhaled air.
Note: It is important to instruct the patient to:
• carefully read the instructions for use contained in the package leaflet contained in each package of Symbicort Turbohaler Inhaler;
• breathe in forcefully and deeply through the mouthpiece to ensure that the optimal dose reaches the lungs;
• never exhale through the mouthpiece;
• replace the cap on the Symbicort Turbohaler Inhaler after use;
• rinse your mouth with water after inhaling the maintenance dose to minimize the risk of oropharyngeal candidiasis. If oropharyngeal candidiasis occurs, patients should rinse their mouth with water even after reliever inhalations.
The patient may not experience any taste or sensation of medicine while using Symbicort Turbohaler Inhaler due to the small amount of medicine that is administered.
04.3 Contraindications
Hypersensitivity (allergy) to budesonide, formoterol or lactose (which contains small amounts of milk protein).
04.4 Special warnings and appropriate precautions for use
A gradual decrease in dosage is recommended when ending treatment, which should not be stopped abruptly.
If patients find treatment ineffective or if they exceed the higher recommended doses of Symbicort, medical advice should be sought (see section 4.2). Sudden and progressive worsening in the control of asthma or COPD are potentially life threatening and the patient should undergo an emergency medical examination. In this situation, consideration should be given to the need to increase corticosteroid therapy, for example to a course of oral corticosteroids or to initiate antibiotic treatment in case of infection.
Patients should be advised to have their own reliever inhaler available at all times, either Symbicort (for asthma patients taking Symbicort as maintenance and reliever therapy) or a separate fast-acting bronchodilator (for all patients taking Symbicort) Symbicort as maintenance therapy only).
Patients should be reminded to take their Symbicort maintenance dose, as prescribed, even in the absence of symptoms. The prophylactic use of Symbicort, for example before physical exercise, has not been studied. Symbicort reliever inhalations should be taken in response to asthma symptoms but are not intended for regular prophylactic use, for example before a physical exercise. Another fast-acting bronchodilator should be considered for this use.
Once asthma symptoms are under control, tapering of the dose of Symbicort may be considered. Regular monitoring of patients is important when treatment begins to include dose reductions. The lowest effective dose of Symbicort should be used. (see section 4.2).
Patients should not initiate Symbicort therapy during an exacerbation, or if they have significant worsening or acute deterioration of asthma.
Serious asthma-related adverse events and exacerbations may occur during treatment with Symbicort. Patients should be asked to continue treatment but also to seek medical advice if asthma symptoms remain uncontrolled or worsen after initiation of therapy. with Symbicort.
As with other inhalation therapies, paradoxical bronchospasm may be observed, with an immediate increase in wheezing and shortness of breath after intake. If the patient experiences paradoxical bronchospasm Symbicort should be discontinued immediately, the patient should be evaluated and, if necessary, instituted. alternative therapy Paradoxical bronchospasm responds to inhalation of fast-acting bronchodilators and should be treated immediately (see Section 4.8).
Systemic effects can occur with any inhaled corticosteroid, especially at high doses and prescribed for long periods. These effects are much less likely to occur with inhaled treatment than with oral corticosteroids.
Possible systemic effects include Cushing's syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, decreased bone mineral density, cataracts and glaucoma, and more rarely a range of psychological or behavioral effects including psychomotor hyperactivity, sleep, anxiety, depression or aggression (particularly in children) (see section 4.8).
It is recommended to periodically check the height of children on prolonged treatment with inhaled corticosteroids. If growth is slowed, existing therapy should be re-evaluated to reduce the dose of the inhaled corticosteroid to the lowest dose at which effective asthma control is achieved, if possible. The benefits of corticosteroid therapy should be carefully weighed against possible risks of growth suppression. Consideration should also be given to a specialist examination by a pediatric pulmonologist.
Limited data from long-term studies suggest that most children and adolescents treated with inhaled budesonide achieve "adequate adult height. However, an initial, but transient, small decrease in growth (approximately 1 cm), usually during the first year of treatment.
Potential effects on bone density should be considered, especially in patients treated with high doses, for prolonged periods, with coexisting risk factors for the onset of osteoporosis. Long-term studies with inhaled budesonide in children at medium doses daily doses of 400 mcg (delivered dose) or in adults at daily doses of 800 mcg (delivered dose) did not show significant effects on bone mineral density. No information is available on the effect of Symbicort at higher doses.
If there are reasons to suppose that adrenal function is impaired due to previous systemic steroid therapy, care should be taken when initiating Symbicort therapy.
The benefits of inhaled budesonide therapy should normally minimize the need for oral steroids, but patients who are already on oral steroid therapy may remain at risk of adrenal impairment for an extended period of time.
Recovery may take a long time after discontinuation of oral steroid therapy and therefore oral steroid dependent patients switching to inhaled budesonide may remain at risk of impaired adrenal function for a considerable period of time. circumstance, the function of the hypothalamus-pituitary-adrenal axis should be monitored regularly.
Prolonged treatment with high doses of particularly higher than recommended inhaled corticosteroids may also result in clinically significant adrenal suppression. Therefore, additional coverage with systemic corticosteroids should be considered during times of stress such as severe infections or elective surgery. Rapid reduction in steroid dose may induce acute adrenal crisis. Symptoms and signs that may be observed in adrenal crisis acute may be rather vague but may include anorexia, abdominal pain, weight loss, fatigue, nausea, vomiting, decreased level of consciousness, seizures, hypotension, hypoglycemia.
Treatment with additional systemic steroids or inhaled budesonide should not be stopped suddenly.
Generally mild systemic steroid activity may occur during the transition from oral therapy to Symbicort which may result in the onset of allergic or arthritic symptoms such as rhinitis, eczema or muscle and joint pain. Specific treatment should be initiated in these cases. The systemic effect of glucocorticosteroid deficiency should be suspected in rare cases if symptoms such as fatigue, headache, nausea and vomiting occur. In these cases, a temporary increase in glucocorticosteroid dose is sometimes necessary.
To minimize the risk of oropharyngeal candida infection, the patient should be instructed to rinse their mouth with water after inhaling the maintenance dose. If oropharyngeal candidiasis occurs, patients should also rinse their mouth with water after inhalation. as needed.
Concomitant treatment with itraconazole, ritonavir or other potent CYP3A4 inhibitors should be avoided (see section 4.5). If this is not possible, the time interval between administering the interacting drugs should be as long as possible.
In patients using potent CYP3A4 inhibitors, Symbicort maintenance and reliever therapy is not recommended.
Symbicort should be administered with caution in patients with thyrotoxicosis, pheochromocytoma, diabetes mellitus, untreated hypokalaemia, obstructive hypertrophic cardiomyopathy, idiopathic subvalvular aortic stenosis, severe hypertension, aneurysm or other severe cardiovascular disorders such as cardiac ischaemia, severe tachyarrhythmia.
Caution should be exercised when treating patients with QTc interval prolongation. Formoterol itself may induce QTc interval prolongation.
The need and dose of inhaled corticosteroids should be re-evaluated in patients with active or quiescent pulmonary tuberculosis, fungal and viral airway infections.
Potentially severe hypokalaemia can be caused by high doses of β2-adrenoceptor agonists. The effect of concomitant treatment with β2-adrenoceptor agonists and drugs that can induce hypokalaemia or potentiate a hypokalaemic effect, such as xanthine derivatives, steroids and diuretics, may add to a possible hypokalaemic effect of β2-adrenoceptor agonists.Particular caution is recommended in unstable asthma requiring variable use of emergency bronchodilators, in severe acute asthma, since the risk of hypokalaemia may be increased by hypoxia and in other conditions in which the likelihood of hypokalaemia is increased. In such circumstances it is recommended that serum potassium levels be monitored.
As with all β2-adrenoceptor agonists, additional blood glucose level checks should be performed in diabetic patients.
Symbicort contains lactose monohydrate (lactose intolerance. The lactose excipient contains small amounts of milk proteins which can cause allergic reactions.
04.5 Interactions with other medicinal products and other forms of interaction
Pharmacokinetic interactions
Potent CYP3A4 inhibitors (eg ketoconazole, itraconazole, voriconazole, posaconazole, clarithromycin, telithromycin, nefazodone and HIV protease inhibitors) can markedly increase the plasma levels of budesonide and concomitant use should be avoided. If this is not possible, the time interval between administration of the inhibitor and budesonide should be as long as possible (see section 4.4). In patients using potent CYP 3A4 inhibitors, Symbicort maintenance and reliever therapy is not recommended.
Administration of 200 mg once daily of ketoconazole, a potent inhibitor of CYP3A4, increased the plasma levels of co-administered oral budesonide (single 3 mg dose) by six-fold on average. When ketoconazole was administered 12 hours after budesonide, the concentration increased on average only three-fold showing that extending the timing of administration may reduce the increase in plasma levels. Limited data on this interaction for high-dose inhaled budesonide indicate that marked increases in plasma levels (on average four-fold) may occur if itraconazole, 200 mg once daily, is co-administered with inhaled budesonide (dose single of 1000 mcg).
Pharmacodynamic interactions
Beta-adrenergic blockers may weaken or inhibit the effect of formoterol. Therefore, Symbicort should not be administered concomitantly with beta-adrenergic blockers (including eye drops) unless necessary.
Concomitant treatment with quinidine, disopyramide, procainamide, phenothiazines, antihistamines (terfenadine), monoamine oxidase inhibitors and tricyclic antidepressants may prolong the QTc interval and increase the risk of ventricular arrhythmias.
Furthermore, L-dopa, L-thyroxine, oxytocin and alcohol can impair cardiac tolerance towards β2-sympathomimetics.
Concomitant treatment with monoamine oxidase inhibitors including drugs with similar properties such as, furazolidone and procarbazine, may trigger hypertensive crises.
There is a high risk of arrhythmias in patients undergoing concomitant halogenated hydrocarbon anesthesia.
Concomitant use of other β-adrenergic or anticholinergic drugs may have a potential additive bronchodilatory effect.
Hypokalaemia may increase the tendency to arrhythmias in patients treated with digitalis glycosides.
No interactions of budesonide and formoterol with other drugs used in the treatment of asthma have been observed.
04.6 Pregnancy and lactation
No clinical data are available on the administration of Symbicort or of formoterol and budesonide administered concurrently in pregnancy. Data from an embryo-fetal development study in the rat showed no evidence of an additional effect due to the combination.
There are no adequate data on the use of formoterol in pregnant women. In animal reproduction studies formoterol caused adverse effects at very high systemic exposure levels (see section 5.3).
Data on approximately 2,000 pregnancies of patients exposed to the use of inhaled budesonide indicate that there is no increased risk of teratogenicity associated with the use of the drug. In animal studies, glucocorticosteroids induced malformations (see section 5.3).
This does not seem relevant to humans in the case of the recommended doses.
Animal studies, at exposures below teratogenic doses, have also identified that an excess of glucocorticoids in prenatal age is involved in the "increased risk of delayed intrauterine growth, cardiovascular disorders in the adult animal, permanent changes in glucocorticoid receptor density, turnover and functionality of neurotransmitters.
Symbicort should only be given during pregnancy if the benefits outweigh the potential risks. Budesonide should be administered at the lowest therapeutically effective dose needed to maintain adequate asthma control.
Budesonide is excreted in breast milk. However, effects on infants are not expected at therapeutic doses. It is not known whether formoterol passes into human breast milk. In rats, small amounts of formoterol were found in breast milk. The administration of Symbicort to women who are breastfeeding should only be considered if the expected benefits to the mother are greater than any possible risk to the baby.
04.7 Effects on ability to drive and use machines
Symbicort has little or no effect on the ability to drive or use machines.
04.8 Undesirable effects
As Symbicort contains both budesonide and formoterol, the same pattern of side effects seen with these substances may occur. No increased incidence of adverse reactions was observed following concomitant administration of the two compounds. The most common drug-related adverse reactions are pharmacologically predictable side effects of β2-agonist therapy, such as tremors and palpitations. These effects tend to be mild and usually disappear within a few days of starting treatment. In a 3-year clinical study with budesonide in COPD, bruising and pneumonia occurred at a frequency of 10% and 6%, respectively, in comparison. to the placebo group which reported a frequency of 4% and 3% (respectively p
Adverse reactions associated with budesonide or formoterol are listed below and listed by system organ class and frequency. Frequencies are defined as: very common (≥1 / 10), common (≥1 / 100,
Table 1
Candida infection in the oropharyngeal tract is due to drug deposition. Advise the patient to rinse the mouth with water after each dose to minimize the risk. Candida infections in the oropharyngeal tract usually respond to treatments with topical anti-fungal agents without the need to discontinue inhaled corticosteroids.
As with other inhalation therapies, paradoxical bronchospasm may occur very rarely, affecting less than 1 in 10,000 people, with wheezing and shortness of breath appearing soon after administration. Paradoxical bronchospasm responds to inhalation of a fast-acting bronchodilator and should be treated immediately. Symbicort should be discontinued immediately, the patient assessed and alternative therapy initiated if necessary (see section 4.4).
Systemic effects may occur with inhalation of corticosteroids, particularly in high doses and prescribed for a long time. These effects occur less frequently than with oral corticosteroids. Possible systemic effects include Cushing's syndrome, Cushingoid features, suppression of function adrenal, growth retardation in children and adolescents, decreased bone mineral density, cataracts and glaucoma. Increased susceptibility to infections and impaired ability to adapt to stress may occur. Effects are likely to depend on dose, exposure time, concomitant and previous steroid exposure and individual sensitivity.
Treatment with β2-agonist adrenoceptors can cause an increase in blood levels of insulin, free fatty acids, glycerol and ketone bodies.
04.9 Overdose
An overdose of formoterol would cause typical effects of β2-adrenoceptors agonists: tremor, headache, palpitations. Symptoms reported from isolated cases are tachycardia, hyperglycemia, hypokalaemia, QTc interval prolongation, arrhythmia, nausea and vomiting. Supportive and symptomatic treatments may be indicated. A dose of 90 micrograms of formoterol administered over three hours in patients with Acute bronchial obstructions did not raise safety concerns.
An acute overdose of budesonide, even at very high doses, is not expected to cause clinical problems. If budesonide is used chronically in excessive doses, systemic effects of glucocorticosteroids such as hypercorticism and adrenal suppression may occur.
Adequate therapy with an inhaled corticosteroid should be considered if Symbicort therapy is discontinued due to an overdose of formoterol (component of the combination).
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: adrenergics and other drugs for obstructive respiratory tract syndromes.
ATC code: R03AK07
Mechanisms of action and pharmacodynamic effects
Symbicort contains formoterol and budesonide, which exhibit different mechanisms of action and exhibit additive effects in terms of reducing asthma exacerbations. The specific properties of budesonide and formoterol allow the combination to be used as both maintenance and reliever therapy and as a maintenance treatment for asthma.
Budesonide
Budesonide is a glucocorticoid which when inhaled has a dose-dependent anti-inflammatory action on the respiratory tract, resulting in a reduction in symptoms and fewer asthma exacerbations. Inhaled budesonide has fewer serious adverse effects than systemic administration of corticosteroids. The exact mechanism of action responsible for the anti-inflammatory effect of glucocorticoids is not known.
Formoterol
Formoterol is a selective β2-adrenoceptor agonist which when inhaled produces rapid and prolonged relaxation of bronchial smooth muscle in patients with reversible airway obstruction. The bronchodilator effect is dose dependent, with an onset of effect within 1-3 minutes. The duration of the effect is at least 12 hours after a single dose.
Budesonide / formoterol
Asthma
Clinical efficacy of budesonide / formoterol maintenance therapy
Clinical studies in adults have shown that adding formoterol to budesonide improved asthma symptoms and lung function, and reduced exacerbations. In two 12-week studies, the effect on lung function of budesonide / formoterol was equal to that of a free combination of budesonide and formoterol and superior to that of budesonide alone. A β2 - was used as needed in all treatment groups. Short-acting agonist adrenoceptor There was no sign of attenuation of the antiasthmatic effect over time.
In a 12-week pediatric study, 85 children aged 6 to 11 years were treated with the maintenance dose of budesonide / formoterol (2 inhalations of 80 mcg / 4.5 mcg / inhalation twice / day) and with short-acting β2-adrenoceptor agonist as needed. Lung function improved and treatment was well tolerated compared to the corresponding dose of budesonide taken alone.
Clinical efficacy of budesonide / formoterol maintenance and reliever therapy
A total of 12076 patients with asthma were involved in 5 double-blind clinical studies of efficacy and safety (4447 were randomized to maintenance and reliever therapy with budesonide / formoterol) of 6 or 12 months duration. Patients were to be symptomatic despite daily use of inhaled glucocorticoids.
Budesonide / formoterol maintenance and reliever therapy resulted in clinically and statistically significant reductions in severe exacerbations compared to all comparator treatments in all 5 studies. These include a comparison of budesonide / formoterol at the highest maintenance dose with terbutaline as needed (in study 735) and budesonide / formoterol at the same maintenance dose with either formoterol or terbutaline as needed (study 734) (Table 2). In study 735, lung function, symptom control, and reliever use were similar in all treatment groups. In study 734, symptoms and reliever use were reduced and lung function improved, compared to both. comparison treatments. In the 5 studies reviewed together, patients taking budesonide / formoterol maintenance and reliever therapy did not use reliever inhalations on average on 57% of treatment days. There was no evidence of tolerance development over time.
Table 2 Summary of severe exacerbations in clinical trials
a Hospitalization / emergency treatment or treatment with oral steroids
bThe reduction in the rate of exacerbations is statistically significant (value of P.
In 2 other studies involving patients requiring medical attention for acute asthma symptoms, budesonide / formoterol induced a rapid and effective reduction in bronchoconstriction similar to salbutamol and formoterol.
COPD
The effect on lung function and the frequency of exacerbations (defined as cycles of oral steroids and / or antibiotics and / or hospitalizations) was evaluated in two 12-month studies in patients with severe COPD. The median FEV1 at all. "inclusion in the studies was 36% of normal. The mean number of exacerbations / year (as defined above) was significantly reduced with budesonide / formoterol compared to treatment with formoterol alone or placebo (mean frequency 1.4 versus 1.8-1.9 in the placebo / formoterol). The mean number of days of oral corticosteroid therapy / patient over 12 months was slightly reduced in the budesonide / formoterol group (7-8 days / patient / year versus 11-12 and 9-12 days in the placebo and formoterol groups, respectively) . Budesonide / formoterol was not superior to formoterol treatment alone with respect to changes in lung function parameters such as FEV1.
05.2 Pharmacokinetic properties
Absorption
The combination of a fixed dose of budesonide and formoterol, and the corresponding monoproducts have been shown to be bioequivalent in relation to the systemic exposure of budesonide and formoterol, respectively. Despite this, a slight increase in cortisol suppression was observed after administration of the fixed combination compared to the monoproducts. The difference is considered to have no impact on clinical safety.
There is no evidence of pharmacokinetic interactions between budesonide and formoterol.
The pharmacokinetic parameters for the respective substances were comparable after administration of budesonide and formoterol as monoproducts or as a combination of a fixed dose. For budesonide, the AUC was slightly higher, the absorption rate faster, and the peak plasma concentration higher after administration of the fixed combination. For formoterol, the peak plasma concentration was similar after administration of the fixed combination. .Inhaled budesonide is rapidly absorbed and the peak plasma concentration is reached within 30 minutes after inhalation. In studies, the mean lung deposition of budesonide after inhalation via inhaler ranged from 32% to 44% of the inhaled dose. Systemic bioavailability is approximately 49% of the delivered dose In children 6 to 16 years of age, lung deposition is within the same range as in adults for the same administered dose The resulting plasma concentrations have not been determined.
Inhaled formoterol is rapidly absorbed and the peak plasma concentration is reached within 10 minutes after inhalation. In studies, the mean lung deposition of formoterol following inhalation via the powder inhaler ranged from 28% to 49% of the inhaled dose. Systemic bioavailability is approximately 61% of the inhaled dose.
Distribution and metabolism
Plasma protein binding is approximately 50% for formoterol and 90% for budesonide. The volume of distribution is approximately 4 L / kg for formoterol and 3 L / kg for budesonide. Formoterol is inactivated by conjugation reactions (O-demethylated and deformed active metabolites are formed, mostly detected as inactive conjugates). Budesonide undergoes an extensive degree (approximately 90%) of biotransformation to metabolites with low glucocorticosteroid activity on the first hepatic pass. The glucocorticosteroid activity of the major metabolites, 6-beta-hydroxy-budesonide and 16-alpha-hydroxy-prednisolone, is less than 1% of that of budesonide. There is no indication of any metabolic or receptor interaction between formoterol and budesonide.
Elimination
The major part of a dose of formoterol is transformed by hepatic metabolism followed by renal elimination. Following inhalation, 8% to 13% of the inhaled dose of formoterol is excreted unmetabolized in the urine. Formoterol has a high level of systemic elimination (approximately 1.4 l / min) and the terminal half-life averages 17 hours.
Budesonide is eliminated by metabolism mainly catalysed by the CYP3A4 enzyme. The metabolites of budesonide are excreted in the urine as such or in conjugated form. Only negligible levels of unchanged budesonide have been found in the urine. Budesonide has a "high systemic elimination (approximately). 1.2 l / min) and the plasma elimination half-life after iv administration averages 4 hours.
The pharmacokinetics of budesonide or formoterol in patients with renal insufficiency are unknown. The exposure of budesonide and formoterol may be increased in patients with hepatic impairment.
05.3 Preclinical safety data
The toxicity observed in animal studies with budesonide and formoterol, given in combination or separately, is due to effects associated with exaggerated pharmacological activity.
In animal reproduction studies, corticosteroids such as budesonide have been shown to induce malformations (cleft palate, skeletal malformations). However, these experimental results in animals do not seem relevant in humans if the recommended doses are adhered to. Animal reproduction studies with formoterol have shown some reduction in fertility in male rats after high systemic exposure and loss of embryonic implants, as seen, at a much higher systemic exposure than that achieved during clinical use. increased postnatal mortality and reduced birth weight. However, these experimental results in animals do not seem relevant in humans.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Lactose monohydrate (containing milk proteins)
06.2 Incompatibility
Not relevant.
06.3 Period of validity
2 years.
06.4 Special precautions for storage
Do not store above 30 ° C. Keep the container tightly closed to protect the medicine from moisture.
06.5 Nature of the immediate packaging and contents of the package
Symbicort is a multidose powder inhaler, operated by the inspiratory flow.
The inhaler is white with a red rotating ring and is made of different plastic materials (PP, PC, HDPE, LDPE, LLDPE, PBT). In each secondary pack there are 1, 2, 3, 10 or 18 inhalers containing 60 (or 120) doses Not all pack sizes may be marketed.
06.6 Instructions for use and handling
No special instructions.
07.0 MARKETING AUTHORIZATION HOLDER
AstraZeneca S.p.A.
Volta Palace, Via F. Sforza
20080 Basiglio (Milan)
08.0 MARKETING AUTHORIZATION NUMBER
Symbicort Turbohaler 1 inhaler of 60 doses 160 / 4.5 mcg: A.I.C. 035194012 / M
Symbicort Turbohaler 2 inhalers of 60 doses 160 / 4.5 mcg: A.I.C. 035194048 / M
Symbicort Turbohaler 3 inhalers of 60 doses 160 / 4.5 mcg: A.I.C. 035194036 / M
Symbicort Turbohaler 10 inhalers of 60 doses 160 / 4.5 mcg: A.I.C. 035194024 / M
Symbicort Turbohaler 18 inhalers of 60 doses 160 / 4.5 mcg: A.I.C. 035194051 / M
Symbicort Turbohaler 1 inhaler of 120 doses 160 / 4.5 mcg: A.I.C. 035194063 / M
Symbicort Turbohaler 2 inhalers of 120 doses 160 / 4.5 mcg: A.I.C. 035194087 / M
Symbicort Turbohaler 3 inhalers of 120 doses 160 / 4.5 mcg: A.I.C. 035194075 / M
Symbicort Turbohaler 10 inhalers of 120 doses 160 / 4.5 mcg: A.I.C. 035194099 / M
Symbicort Turbohaler 18 inhalers of 120 doses 160 / 4.5 mcg: A.I.C. 035194101 / M
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
May 2001 / August 2005
10.0 DATE OF REVISION OF THE TEXT
February 2012
