Active ingredients: Beclometasone dipropionate anhydrous, Formoterol fumarate dihydrate
FORMODUAL 100 micrograms / 6 micrograms inhalation powder
Indications Why is Formodual used? What is it for?
FORMODUAL is a powder that is inhaled through the mouth and released directly into the lungs. Contains two active ingredients: anhydrous beclomethasone dipropionate and formoterol fumarate dihydrate.
- Anhydrous beclomethasone dipropionate belongs to a group of medicines commonly referred to as steroids (technically corticosteroids). Steroids are able to treat and prevent asthma symptoms. They have an anti-inflammatory action, thereby reducing swelling and irritation of the walls of the small airways in the lungs.
- Formoterol fumarate dihydrate belongs to a group of medicines called long-acting bronchodilators, which relax the muscles of the airways by dilating them, thus making it easier to breathe in and out of the lungs.
Together, these two active ingredients facilitate breathing, providing relief from symptoms such as shortness of breath, wheezing and coughing in patients with asthma or COPD and also help prevent asthma symptoms.
Asthma
FORMODUAL is used for the treatment of asthma in adults.
If you have been prescribed FORMODUAL it is likely that:
- asthma is not adequately controlled using inhaled corticosteroids and short-acting "as-needed" bronchodilators, or
- asthma responds well to treatment with both corticosteroids and long-acting bronchodilators.
COPD
FORMODUAL can also be used to treat the symptoms of severe chronic obstructive pulmonary disease (COPD) in adult patients. COPD is a chronic airway disease of the lungs, mainly caused by cigarette smoking.
Contraindications When Formodual should not be used
Do not use FORMODUAL
If you are allergic to beclomethasone dipropionate anhydrous or formoterol fumarate dihydrate or any of the other ingredients of this medicine (listed in section 6).
Precautions for use What you need to know before taking Formodual
Do not take this medicine to treat acute asthma symptoms such as wheezing, wheezing and coughing or if your asthma is getting worse or to treat acute asthma attacks. To treat your symptoms you should use your fast-acting "reliever" inhaler which you should always carry with you.
Talk to your doctor before using FORMODUAL if you have any of the following conditions:
- heart problems, which include any type of known disease of the heart and / or heart function
- heart rhythm disturbances, such as increased or irregular heart rate, fast pulse or palpitations, or if you have been told that your heart pattern is abnormal
- high blood pressure
- narrowing of the arteries (also known as arteriosclerosis), or if you know that you have an aneurysm (an abnormal dilation of blood vessel walls)
- overactive thyroid gland
- low levels of potassium in the blood
- any liver or kidney problems
- diabetes. If you inhale high doses of formoterol, your blood glucose levels may rise and as a result you may need to carry out additional tests to monitor your blood sugar level both when you start using this inhaler and periodically throughout the duration of treatment.
- adrenal gland tumor (called pheochromocytoma)
- if you need to undergo anesthesia. Depending on the type of anesthesia, it may be necessary to stop taking FORMODUAL at least 12 hours before the anesthesia.
- If you are taking, or have taken, medicines to treat tuberculosis (TB), or if you have known viral infections or chest fungal infections.
If any of the above apply to you, always tell your doctor before using FORMODUAL.
If you are not sure whether you can use FORMODUAL talk to your doctor, asthma nurse or pharmacist before using the inhaler.
Interactions Which drugs or foods may change the effect of Foster
Before starting treatment, tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including any other inhaler and non-prescription medicines. This is necessary because FORMODUAL can affect the action of other medicines. Also, other medicines can affect the way Foster's work.
Do not use this medicine together with beta blockers. Beta blockers are medicines used to treat various conditions, including heart problems, high blood pressure or glaucoma (increased pressure in the eye). If you use beta-blockers (including eye drops), the effect of formoterol may be reduced or canceled.
Using FORMODUAL together with the following medicines:
- other drugs with activity similar to that of formoterol (ie beta-adrenergic drugs, commonly used to treat asthma)
- quinidine, disopyramide, procainamide (to treat abnormal heart rhythms)
- some antihistamines, for example terfenadine (to treat allergic reactions)
- monoamine oxidase inhibitors or tricyclic antidepressants, for example phenelzine, isocarboxazide, amitriptyline and imipramine; phenothiazines (to treat depression or mental disorders)
- L-DOPA (for the treatment of Parkinson's disease)
- L-thyroxine (to treat an underactive thyroid)
- Medicines containing oxytocin (which causes uterine contractions)
- Monoamine oxidase inhibitors (MAOIs) (for the treatment of mental disorders), including drugs with properties similar to furazolidone and procarbazine
- digoxin (to treat heart disease)
- Other medicines to treat asthma (theophylline, aminophylline or steroids)
- diuretics (tablets to urinate)
- Some anesthetics
FORMODUAL with alcohol
You should avoid consuming alcohol without first talking to your doctor. Alcohol may lower cardiac tolerance to one of the active substances in FORMODUAL, formoterol.
Warnings It is important to know that:
Your doctor may decide to periodically measure your blood potassium levels, especially if your asthma is severe. Like many bronchodilators, FORMODUAL can cause a sharp drop in serum potassium levels (hypokalaemia).This is because a reduction in blood oxygen associated with some other treatments taken together with Fostair can make the reduction in potassium levels worse.
If you have been taking high doses of inhaled corticosteroids for long periods of time, you may need more corticosteroids in stressful situations. Stressful situations may include being hospitalized following an accident, having sustained serious injuries or the period before a "surgery. In such cases, your doctor will decide whether or not to increase your corticosteroid dosage and may prescribe steroids in tablets or steroids for injection.
If you need to be hospitalized, remember to take all your medicines and inhalers with you, including FORMODUAL and any medicines or tablets bought without a prescription, in their original packaging if possible.
Children and adolescents
This medicine should not be given to children and adolescents under the age of 18.
Pregnancy and breastfeeding
There are no clinical data on the use of FORMODUAL during pregnancy.
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before using this medicine. FORMODUAL should only be used during pregnancy if your doctor advises you to do so. Your doctor will decide if you should stop taking FORMODUAL while breastfeeding or if you should take FORMODUAL but refrain from breastfeeding. Always follow your doctor's advice carefully.
Driving and using machines
FORMODUAL is unlikely to affect the ability to drive or use machines.
However, if you notice side effects such as dizziness and / or tremor, your ability to drive or use machines may be impaired.
FORMODUAL contains lactose monohydrate
The excipient lactose monohydrate contains small amounts of milk proteins, which can cause reactions in allergic patients.
For those who play sports:
The use of the drug without therapeutic necessity constitutes doping and can in any case determine positive anti-doping tests.
Dose, Method and Time of Administration How to use Formodual: Posology
Always use this medicine exactly as your doctor, nurse or pharmacist has told you. If you are unsure, ask your doctor or pharmacist.
FORMODUAL delivers an extra-fine powder, which allows more of the drug contained in the dose to reach the lungs. Your doctor may then prescribe you a lower dose of this inhalation medication than you were taking with other inhalers.
Asthma
Your doctor will monitor you regularly to make sure you are taking the correct dose of Foster. Once your asthma is well controlled, your doctor may deem it appropriate to gradually reduce the dose of FORMODUAL. Under no circumstances should you change the dose without first consulting your doctor.
How much FORMODUAL to use:
Adults and the elderly:
The recommended dose of this medicine is 1 or 2 inhalations twice a day.
The maximum daily dose is 4 inhalations.
Do not increase the dose.
If you think the medicine is not working, always talk to your doctor before increasing the dose.
Chronic Obstructive Pulmonary Disease (COPD)
Adults and the elderly:
The recommended dose is two inhalations in the morning and two inhalations in the evening.
Remember: you should always carry your fast-acting "rescue" inhaler with you to treat a worsening of symptoms or a sudden asthma attack.
How to use FORMODUAL:
FORMODUAL is for inhalation use.
In this pack you will find an inhaler, called Nexthaler, enclosed in a heat-sealed protective pouch, which contains the medicine in the form of a powder. The Nexthaler inhaler allows you to inhale the medicine.
If possible, stand or sit upright as you inhale.
If you forget to use FORMODUAL
Take the missed dose as soon as you remember. If it is almost time for your next dose, skip the missed dose and take the next one at the correct time. Do not take a double dose.
If you stop taking FORMODUAL:
Even if you feel better, do not stop using FORMODUAL or decrease its dosage. If you intend to do this, talk to your doctor. It is very important that FORMODUAL is used every day, as prescribed by the doctor, even in the absence of symptoms.
If your breathing remains unchanged:
If your symptoms do not improve after inhaling FORMODUAL, it is possible that you are using the device incorrectly. Therefore check the instructions for proper use of the device at the end of this leaflet and / or contact your doctor or nurse to explain how to use it properly.
If your asthma gets worse
: If your symptoms worsen or are difficult to control (for example if you use your "reliever" inhaler more frequently), or if your "reliever" inhaler does not improve your symptoms, you should continue to use FORMODUAL but contact your doctor as soon as possible. Your doctor may decide to change your dose of Fostair or prescribe an additional or alternative treatment.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
Overdose What to do if you have taken too much Formodual
- Contact your doctor or the nearest hospital emergency department immediately for advice. Take the medicine with you so that the healthcare professional can understand which medicine you have taken;
- Undesirable effects may occur. Tell your doctor if you notice any unusual symptoms, as you may need to investigate further or take any necessary treatment measures.
Side Effects What are the side effects of Formodual
Like all medicines, this medicine can cause side effects, although not everybody gets them.
As with other inhaled treatments, there is a risk of worsening wheezing, coughing and wheezing immediately after use of FORMODUAL, and this is referred to as paradoxical bronchospasm. If this occurs, you should STOP using it immediately. of FORMODUAL and use your fast-acting 'reliever' inhaler as soon as possible to treat your symptoms. You should contact your doctor immediately.
Tell your doctor immediately if you have any allergic reactions, which include skin allergies, itchy skin, rash, red skin, swelling of the skin or mucous membranes, especially of the eyes, face, lips and throat.
Further possible side effects of FORMODUAL are listed below in order of frequency.
Contact your doctor or pharmacist immediately:
- if you experience any of the side effects listed below and if these effects cause you distress or are severe in intensity or persist for several days
- if he is worried for some reason or if there is something he does not understand.
Your doctor will assess your degree of asthma and start another course of treatment if necessary.
You may be told not to use FORMODUAL again.
Common (may affect up to 1 in 10 people):
- tremor.
- pneumonia (infection of the lung), in patients with COPD
Tell your doctor if you have any of the following symptoms while taking Fostair, they could be symptoms of a lung infection:
- fever or chills.
- increased mucus production, mucus color changes.
- increased cough or difficulty breathing.
Uncommon (may affect up to 1 in 100 people):
- cold symptoms, sore throat
- fungal infections (of the mouth and throat). Rinsing your mouth or gargle with water and brushing your teeth immediately after inhaling can help prevent these unwanted effects.
- worsening of asthma symptoms, difficulty breathing
- hoarseness
- cough - unusually fast heartbeat
- unusually slow heartbeat
- oppressive pain in the chest
- headache
- feeling of being unwell
- feeling tired or nervous
- alteration in the electrocardiogram (ECG)
- low level of cortisol in the urine or blood
- high level of potassium in the blood
- high blood glucose level
- high level of fat in the blood.
Side effects seen with similar inhaled medicinal products containing beclomethasone dipropionate and / or formoterol are:
- palpitations - uneven heartbeat
- abnormal or altered taste
- muscle pain and muscle cramps
- restlessness, dizziness
- feeling anxious
- sleep disorders
- drop in the level of potassium in the blood
- increase / decrease in blood pressure.
The use of inhaled corticosteroids in high doses and for long periods of time can cause systemic effects, including:
- disturbances in the function of the adrenal glands (adrenal suppression)
- thinning of the bones
- growth retardation in children and adolescents
- increased pressure in the eye (glaucoma), cataracts
- rapid weight gain, particularly in the face and torso
- sleep disturbances, depression or worry, agitation, nervousness, overexcitation or irritability. These effects are more likely to occur in children.
- Abnormal behavior.
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system at www.agenziafarmaco.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 medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton, envelope and label after EXP. The expiry date refers to the last day of that month.
Store in the original package to protect from moisture. Remove the inhaler from its protective pouch only immediately before its first use.
Before opening the envelope for the first time:
This medicinal product does not require any special storage temperatures.
After the first opening of the pouch:
Do not store above 25 ° C.
After first opening the sachet, the medicine must be used within 6 months.
Use the label on the box to write the date the envelope was opened.
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.
Deadline "> Other information
What FORMODUAL contains
The active ingredients are: anhydrous beclomethasone dipropionate and formoterol fumarate dihydrate.
Each pre-dispensed dispensing contains 100 micrograms of anhydrous beclomethasone dipropionate and 6 micrograms of formoterol fumarate dihydrate. This corresponds to an inhaled dose delivered through the mouthpiece of 81.9 micrograms of anhydrous beclomethasone dipropionate and 5 micrograms of formoterol fumarate dihydrate.
The other ingredients are: lactose monohydrate (which contains small amounts of milk proteins) and magnesium stearate.
Description of how FORMODUAL looks and contents of the pack
This medicine comes as a white or almost white inhalation powder contained in a plastic inhaler called Nexthaler.
Each pack contains one, two or three inhalers providing 120 inhalations each.
Each inhaler is packaged in a heat-sealed protective pouch (aluminum foil packaging).
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 -
FORMODUAL 100/6 MCG FOR DISPENSING PRESSURIZED SOLUTION FOR INHALATION
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION -
Each dispensing (from the dosing valve) contains:
100 mcg of beclomethasone dipropionate and 6 mcg of formoterol fumarate dihydrate.
This is equivalent to an inhaled dose (from the mouthpiece) of 84.6 mcg of beclomethasone dipropionate and 5.0 mcg of formoterol fumarate dihydrate.
For the full list of excipients see section 6.1.
03.0 PHARMACEUTICAL FORM -
Pressurized solution for inhalation.
04.0 CLINICAL INFORMATION -
04.1 Therapeutic indications -
Asthma
Formodual is indicated in the regular treatment of asthma when the use of a combination product (inhaled corticosteroid and long-acting beta2-agonist) is appropriate:
- in patients inadequately controlled on inhaled corticosteroids and inhaled fast-acting beta2-agonists used "as needed" or
- in patients who are already adequately controlled on both inhaled corticosteroids and long-acting beta2-agonists.
Chronic Obstructive Pulmonary Disease (COPD)
Symptomatic treatment of patients with severe COPD (FEV1 important symptoms despite regular therapy with long-acting bronchodilators.
04.2 Posology and method of administration -
Formodual is for inhalation use.
Dosage
ASTHMA
Formodual is not indicated for the initial treatment of asthma. The dosage of the components of Formodual varies from patient to patient and must be adapted according to the severity of the disease. association, but also when the dosage is changed. Should a patient require a combination of doses other than those available with the fixed combination, the appropriate doses of beta2-agonists and / or corticosteroids should be prescribed in separate inhalers.
The beclomethasone dipropionate present in the Formodual is characterized by a distribution of extrafine particles such as to determine a more powerful effect than the formulations of beclomethasone dipropionate with a distribution of non-extrafine particles (100 mcg of extrafine beclomethasone dipropionate in the Formodual are equivalent to 250 mcg of beclomethasone dipropionate in non-extra-fine formulation). Therefore, the total daily dose of beclomethasone dipropionate administered by Formodual should be less than the total daily dose of beclomethasone dipropionate administered by a non-extrafine formulation of beclomethasone dipropionate.
This should be taken into account when a patient switches from a non-extrafine formulation of beclomethasone dipropionate to Formodual; the dose of beclomethasone dipropionate should be lower and it will need to be adapted to the individual needs of the patient.
There are two methods of treatment:
A. Maintenance therapy: Formodual is taken as a regular maintenance treatment with another fast-acting bronchodilator to be used as needed.
B. Maintenance and reliever therapy: Formodual is taken as both regular maintenance and reliever treatment in response to asthma symptoms.
A. Maintenance therapy
Patients should be advised to always have the other fast-acting bronchodilator available for emergency use.
Recommended dosage for adults aged 18 and over:
One or two inhalations twice a day.
The maximum daily dose is 4 inhalations.
B. Maintenance and reliever therapy
Patients take a daily maintenance dose of Foster and also take Foster as needed in response to asthma symptoms. Patients should be advised to always have Foster available for reliever use.
Foster maintenance and reliever therapy should especially be considered for patients with:
• inadequate asthma control and the need for 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 Foster as-needed inhalations.
Recommended dosage for adults aged 18 and over :
The recommended maintenance dose is 1 inhalation twice a day (one inhalation in the morning and one inhalation in the evening).
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.
The maximum daily dose is 8 inhalations.
Patients requiring frequent daily use of reliever inhalations should be strongly advised to seek medical advice. Their asthmatic condition should be re-evaluated and their maintenance therapy should be reconsidered.
Recommended dosage for children and adolescents under 18 years:
The safety and efficacy of Formodual in children and adolescents aged below 18 years have not yet been established. There are no data available on the use of Formodual in children below 12 years of age. Only limited data are available in adolescents aged 12-17 years. Therefore, until further data become available, the use of Formodual in children and adolescents below 18 years is not recommended.
Patients should be monitored regularly by their doctor to ensure that the dosage of Foster remains optimal and that it is only changed on the advice of the doctor. The dose should be adjusted to the lowest dose sufficient to maintain effective symptom control.
Once symptom control is achieved with the lowest recommended dosage, inhaled corticosteroid alone can be tried as the next step.
Patients should be advised to take Formodual every day, even when asymptomatic.
COPD
Recommended dosage for adults aged 18 and over:
Two inhalations twice a day.
Special patient groups:
There is no need to adjust the dosage in elderly patients. There are no data available on the use of Formodual in patients with impaired renal or hepatic function (see section 5.2).
Method of administration
To ensure correct administration of the medicine, a doctor or healthcare professional must show the patient how to use the inhaler correctly.
Correct use of the pressurized inhaler is essential for successful treatment.
The patient should be advised to read the package leaflet carefully and follow the instructions for use described therein.
The Formodual inhaler is equipped with a dose counter on the back of the dispenser, which indicates the number of doses left. For the 120 dispensing pack, each time the patient presses the can, a dose of medicine is dispensed and the dose counter then scales by a number. For the pack of 180 puffs, each time the patient presses the can the dose counter scales by a small amount and the number of doses remaining is displayed in intervals of 20. Patients should be warned not to drop the inhaler, as this can cause the activation of the step-by-step numbering of the dose counter.
Check the functioning of the inhaler
Before using the inhaler for the first time or if the inhaler has not been used for 14 days or more, the patient should make a puff into the air to ensure that the inhaler is working properly.
When using the inhaler for the first time, the number 120 or 180 should appear in the dose counter window.
Whenever possible, patients should stand or sit upright when inhaling.
Use of the inhaler
1. Patients should remove the protective cap from the mouthpiece and check that the mouthpiece is clean and free of dust and dirt or any other foreign objects.
2. Patients should exhale as slowly and deeply as possible.
3. Patients should hold the can vertically, with the regulator body upwards, and then place the mouthpiece between their lips tightly closed. Without biting into the mouthpiece.
4. At the same time, patients should inhale slowly and deeply through the mouth. After they start to inhale, they have to press on the top of the inhaler to deliver a dose.
5. Patients should hold their breath for as long as possible and finally take the inhaler away from their mouth and exhale slowly. Patients should not exhale into the inhaler.
To deliver an additional dose, patients should hold the inhaler upright for approximately half a minute and repeat steps 2 to 5.
IMPORTANT: Patients should not perform steps 2 to 5 too quickly.
After use, patients should close the inhaler with the protective cap and check the dose counter.
Patients should be advised to get a new inhaler when the counter or indicator shows the number 20. They should stop using the inhaler when the counter shows the number 0, as the amount of medicine left in the device may not be enough to deliver a full dose.
If after inhalation a mist is observed coming out of the inhaler or from the sides of the mouth, the procedure must be repeated from step 2.
For patients with a weak grip, it may be easier to hold the inhaler with both hands. Then the index fingers should be placed on the top of the inhaler and both thumbs on the base of the inhaler.
After each inhalation, patients should rinse their mouth or gargle with water or brush their teeth (see section 4.4).
CLEANING
Patients should be advised to read the package leaflet carefully for cleaning instructions. For regular cleaning of the inhaler, patients should remove the cap from the mouthpiece and wipe the inside and outside of the mouthpiece with a dry cloth. They should not remove the can from the dispenser and should not use water or other liquids to clean the mouthpiece. mouthpiece.
Patients who have difficulty synchronizing aerosol activation with inspiration can use the AeroChamber Plus spacer device. These patients should be instructed by their doctor, pharmacist or nurse on the proper use and care of their inhaler. and spacer, and their mode of administration should be controlled in order to ensure optimal distribution of the inhaled drug in the lungs.
This result can be achieved by patients using AeroChamber Plus carrying out an inhalation continuously, slowly and deeply through the spacer, without any delay between delivery and inhalation.
04.3 Contraindications -
Hypersensitivity to beclomethasone dipropionate, formoterol fumarate dihydrate or to any of the excipients listed in section 6.1.
04.4 Special warnings and appropriate precautions for use -
Formodual should be used with caution (which may include monitoring) in patients with cardiac arrhythmia, especially in cases of third degree atrioventricular block and tachyarrhythmia (rapid and / or irregular heartbeat), idiopathic subvalvular aortic stenosis, severe obstructive hypertrophic cardiomyopathy. heart disease, in particular acute myocardial infarction, cardiac ischaemia, congestive heart failure, occlusive vascular diseases, in particular arteriosclerosis, arterial hypertension and aneurysm.
Caution should also be exercised when treating patients with known or suspected prolongation of the QTc interval, whether congenital or drug-induced (QTc> 0.44 seconds). Formoterol itself can cause prolongation of the QTc interval.
Caution is also required when Formodual is used by patients with thyrotoxicosis, diabetes mellitus, pheochromocytoma and untreated hypokalaemia.
Therapy with β2-agonist medicinal products has the potential to cause severe hypokalaemia. Particular caution should be exercised in patients with severe asthma as this effect may be potentiated by hypoxia. Hypokalaemia may also be potentiated by concomitant treatments with other medicinal products that can induce hypokalaemia, such as xanthine derivatives, steroids and diuretics (see section 4.5). Caution is also recommended in "unstable asthma, when some" as-needed "bronchodilators may be used. It is recommended that serum potassium levels be monitored in these cases.
Inhalation of formoterol can cause an increase in blood glucose levels. Consequently, blood glucose should be monitored constantly in diabetic patients.
If anesthesia with halogenated anesthetics is to be performed, it must be ensured that Foster is not administered for at least 12 hours before the start of anesthesia, as there is a risk of cardiac arrhythmias.
Like all inhaled medicinal products containing corticosteroids, Formodual should be administered with caution to patients with active or quiescent pulmonary tuberculosis, fungal and viral infections of the respiratory tract.
Treatment with Formodual should not be stopped abruptly.
Close attention should be paid by the physician if the patient does not find the treatment effective. The "increased use of" as needed "bronchodilators indicates a worsening of the underlying condition and justifies a change in therapy. Sudden and progressive worsening of asthma or COPD control is potentially life-threatening and the patient should be urgently evaluated. The need for increased therapy with inhaled or oral corticosteroids should be considered. therapy, or initiate antibiotic therapy if infection is suspected. Patients should not initiate therapy with Foster during an exacerbation or if they have significant worsening or acute deterioration of asthma. Adverse events may occur during therapy with Foster severe asthma-related and exacerbations. Patients should be asked to continue treatment but to seek medical advice if asthma symptoms remain uncontrolled or if they worsen after initiation of Formodual therapy. As with other inhalation therapies paradoxical bronchospasm may occur, with an immediate increase in wheezing and rapid breathing after administration. If this occurs, a fast-acting bronchodilator should be administered immediately by inhalation. Formodual should be discontinued immediately and the patient evaluated and subjected to alternative therapy if necessary. Formodual should not be used as initial asthma therapy. Patients should be advised to always have their fast acting bronchodilator handy for the treatment of acute asthma attacks, which can be either Formodual (for patients taking Formodual as maintenance and reliever therapy) and another fast-acting bronchodilator (for all patients taking Formodual as maintenance therapy only). Patients should be reminded to take Formodual daily as prescribed, even when asymptomatic. Formodual should be taken as needed in response to asthma symptoms, but are not intended for regular prophylactic use, for example prior to physical exercise. Another fast-acting bronchodilator should be considered for this use.
When asthma symptoms are under control, consideration may be given to gradually reducing the dose of Foster. It is important to check patients regularly if treatment is reduced. The lowest effective dose of Formodual should be used (see section 4.2).
Systemic effects may occur with inhaled corticosteroids, particularly when prescribed for prolonged periods and at high doses. These effects are much less likely to occur with inhaled corticosteroids than with oral ones. Possible systemic effects include: Cushing's syndrome, Cushingoid aspect, adrenal suppression, decreased bone mineral density, growth retardation in children and adolescents, cataracts and glaucoma and, more rarely, a range of psychological or behavioral effects including psychomotor hyperactivity , sleep disturbances, anxiety, depression or aggression (particularly in children). It is therefore important that the patient is examined regularly and that the dose of inhaled corticosteroid is the lowest possible dose with which effective control of asthma is maintained.
Single dose pharmacokinetic data (see section 5.2) have shown that the use of FORMODUAL with the AeroChamber Plus spacer device, when compared to the use of the standard dispenser, does not increase the total systemic exposure to formoterol and reduces the systemic exposure to beclomethasone-17-monopropionate; while there is an increase for unchanged Beclometasone dipropionate which reaches the systemic circulation through the lung; however, since the total systemic exposure of Beclometasone dipropionate plus its active metabolite does not change it does not increase the risk of systemic effects when using FORMODUAL with the aforementioned spacer device.
The use of high doses of inhaled corticosteroids for long periods can cause adrenal suppression and acute adrenal crisis. Children under the age of 16 who take / inhale higher than recommended doses of beclomethasone dipropionate may be particularly at risk. which can potentially trigger acute adrenal crises include trauma, surgery, infection or any other case involving a rapid reduction in dosage. Presenting symptoms are typically vague and may include anorexia, abdominal pain, weight loss, fatigue, pain headache, nausea, vomiting, hypotension, decreased level of consciousness, hypoglycemia and seizures. The need for additional systemic corticosteroid coverage should be considered during times of stress or elective surgery. Care should be taken when switching to therapy with Formodual, especially if there is reason to believe adrenal function is impaired by previous systemic steroid therapy.
Patients who have been transferred from oral to inhaled corticosteroid therapy may remain at risk of worsening adrenal reserve for a considerable period of time. Patients who have previously required high-dose emergency corticosteroids or who have been treated for a prolonged period with high-dose inhaled corticosteroids may also be at risk. The possibility of residual impairment in emergency or elective stress-producing situations should always be considered, and appropriate corticosteroid treatment should be considered.
The extent of adrenal impairment may require specialist advice before adopting elective procedures.
Pneumonia in COPD patients
An increased incidence of pneumonia, including pneumonia requiring hospitalization, has been observed in COPD patients treated with inhaled corticosteroids. There is some evidence of an increased risk of pneumonia with increasing steroid dose but this has not been conclusively demonstrated by studies. There is no conclusive clinical evidence of intra-class differences in the magnitude of the risk. of pneumonia among inhaled corticosteroids. Physicians must remain vigilant for the possible development of pneumonia in COPD patients as the clinical manifestations of this type of infections overlap with the symptoms of COPD exacerbations.
Risk factors for pneumonia in COPD patients include smoking, older age, low body mass index (BMI), and severe COPD.
Patients should be advised that Formodual contains a small amount of ethanol (approximately 7 mg per actuation); however at normal dosages the amount of ethanol is irrelevant and does not pose a risk to the patient.
Patients should rinse their mouth or gargle with water or brush their teeth after inhaling the prescribed dose to minimize the risk of oropharyngeal candidiasis infections.
04.5 Interactions with other medicinal products and other forms of interaction -
Pharmacokinetic interactions
Beclomethasone dipropionate metabolizes very rapidly via esterases without involvement of the cytochrome P450 system.
Pharmacodynamic interactions
Avoid using beta-blockers in patients with asthma (including eye drops). If beta-blockers are given for compelling reasons, the effect of formoterol will be reduced or canceled. On the other hand, the concomitant use of other beta-adrenergic drugs may give rise to potentially additive effects, therefore caution is required when prescribing theophylline or other beta-adrenergics at the same time as formoterol.
Simultaneous treatment with quinidine, disopyramide, procainamide, phenothiazines, antihistamines, monoamine oxidase inhibitors and tricyclic antidepressants can cause prolongation of the QTc interval and increase the risk of ventricular arrhythmias.
Furthermore, L-dopa, L-thyroxine, oxytocin and alcohol can alter cardiac tolerance towards beta-2 sympathomimetics.
Concomitant treatment with monoamine oxidase inhibitors, including medicinal products with similar properties such as furazolidone and procarbazine, may cause hypertensive reactions.
There is a high risk of arrhythmias in patients undergoing simultaneous halogenated hydrocarbon anesthesia.
Concomitant treatment with xanthine derivatives, steroids or diuretics may potentiate a possible hypokalaemia effect of beta2-agonists (see section 4.4).
In patients treated with digitalis glycosides, hypokalaemia may increase the predisposition to arrhythmias.
Formodual contains a small amount of ethanol. There is a theoretical possibility of interaction in particularly sensitive patients taking disulfiram or metronidazole.
04.6 Pregnancy and breastfeeding -
There are no experiences or data on the safety of the propellant HFA-134a in pregnancy or lactation in humans. However, studies on the effects of HFA-134a on reproductive function and embryo-fetal development in animals did not reveal clinically relevant adverse events.
Pregnancy
There are no relevant clinical data on the use of Formodual in pregnant women. Animal studies with the combination of beclometasone dipropionate and formoterol have shown signs of reproductive toxicity after high systemic exposure (see section 5.3 Preclinical safety data) Due to the tocolytic effect of beta2-sympathomimetics, particular caution should be exercised during labor. The use of formoterol during pregnancy and particularly late pregnancy or during labor is not recommended unless there is no other (and safer) alternative available. Formodual should only be used during pregnancy if the expected benefits outweigh the potential risks.
Feeding time
There are no relevant clinical data on the use of Formodual in breastfeeding in humans.
Although there are no data in animal experiments, it is reasonable to assume that beclomethasone dipropionate is secreted in breast milk, like other corticosteroids. It is not known whether formoterol passes into breast milk, but it has been found in animal milk.
Administration of Formodual during lactation should only be considered in cases where the expected benefits outweigh the potential risks.
04.7 Effects on ability to drive and use machines -
Formodual is unlikely to affect the ability to drive or use machines.
04.8 Undesirable effects -
As Formodual contains beclomethasone dipropionate and formoterol fumarate dihydrate, adverse reactions expected by type and severity are those associated with each of the two components. There is no incidence of additional adverse events following concomitant administration of the two active substances.
Undesirable effects associated with beclomethasone dipropionate and formoterol, given either as a fixed combination (Formodual) or as individual components, are listed below, listed by organ and system classification.
The frequencies are defined as follows:
very common (≥1 / 10)
common (≥1 / 100 e
uncommon (≥1 / 1,000 and
Common and uncommon adverse reactions result from clinical trial data in asthma and COPD patients.
One non-serious case of pneumonia was reported in a patient treated with Fostair in a pivotal clinical study in COPD patients. Other adverse reactions observed with Formodual in COPD clinical studies were: decreased blood cortisol and atrial fibrillation.
As with other inhalation therapies, paradoxical bronchospasm may occur (see section 4.4 "Special warnings and precautions for use").
Among the adverse reactions observed, those typically associated with formoterol are:
hypokalaemia, headache, tremor, palpitations, cough, muscle spasms and prolongation of the QTc interval.
Adverse reactions typically associated with beclomethasone dipropionate are: oral fungal infections, oral candidiasis, dysphonia, throat irritation.
Dysphonia and candidiasis can be relieved by gargling or rinsing your mouth with water or brushing your teeth after using the product. Symptomatic candidiasis can be treated with topical antifungal therapy while continuing treatment with Formodual.
Systemic effects of inhaled corticosteroids (e.g. beclomethasone dipropionate) may occur particularly when high doses of the medicine are given over long periods of time, and may include: adrenal suppression, decreased bone mineral density, growth retardation in children and adolescents, cataracts and glaucoma (see section 4.4). Hypersensitivity reactions may also occur, including rash, hives, itching, erythema and edema of the eyes, face, lips and throat.
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "address: www.agenziafarmaco.gov.it/it/responsabili.
04.9 Overdose -
Inhalation doses of Formodual up to twelve cumulative actuations (for a total of 1200 mcg beclomethasone dipropionate and 72 mcg formoterol) have been studied in asthmatic patients. These cumulative treatments did not result in abnormal vital signs or particularly serious or severe adverse reactions.
Excessive doses of formoterol may lead to effects that are typical of beta-2 adrenergic agonists: nausea, vomiting, headache, tremor, somnolence, palpitations, tachycardia, ventricular arrhythmia, QTc interval prolongation, metabolic acidosis, hypokalaemia, hyperglycaemia.
In the event of an overdose of formoterol, supportive and symptomatic treatment is indicated. In severe cases, hospitalization is required. The use of cardioselective beta blockers may be considered, but only with extreme caution as they can cause bronchospasm. Serum potassium should be monitored.
Acute inhalations of beclomethasone dipropionate at higher than recommended dosages may result in temporary suppression of adrenal function. In this case, emergency actions are not necessary, as the adrenal function is restored in a few days, as has been verified by the plasma cortisol measurements. In these patients, treatment should be continued with doses sufficient to control asthma.
Chronic overdose of inhaled beclomethasone dipropionate: risk of adrenal suppression (see section 4.4). Monitoring of the adrenal reserve may be necessary. Treatment should be continued with a dosage sufficient to control asthma.
05.0 PHARMACOLOGICAL PROPERTIES -
05.1 "Pharmacodynamic properties -
Pharmacotherapeutic group: Adrenergics and other medicinal products for obstructive airway diseases.
ATC code: R03 AK08.
Mechanism of action and pharmacodynamic effects
Formodual contains beclomethasone dipropionate and formoterol. These two active ingredients have different mechanisms of action. As with other combinations of inhaled corticosteroids and beta2-agonists, additive effects are observed with respect to the reduction of asthma exacerbations.
Beclomethasone dipropionate
Beclomethasone dipropionate administered by inhalation, at recommended doses, has anti-inflammatory activity typical of glucocorticoids in the lung, with consequent reduction of symptoms and exacerbations of asthma, with fewer adverse effects than systemic administration of corticosteroids.
Formoterol
Formoterol is a selective beta-2-adrenergic agonist that produces relaxation of bronchial smooth muscle in patients with reversible airway obstructions. The bronchodilator effect sets in rapidly, within 1-3 minutes after inhalation, and lasts for 12 hours after a single dose.
ASTHMA
Clinical efficacy of Formodual maintenance therapy
The addition of formoterol to beclomethasone dipropionate in clinical trials in adult patients improved asthma symptoms and lung function and reduced exacerbations.
In a 24-week study, the effect of Formodual on lung function was at least equal to that of the impromptu combination of beclometasone dipropionate and formoterol, and was superior to that of beclometasone dipropionate alone.
Clinical efficacy of Formodual maintenance and reliever therapy
A 48-week parallel group clinical study involving 1701 asthma patients compared the efficacy of Formodual given as maintenance therapy (1 inhalation twice daily) and as-needed therapy (up to a total of 8 inhalations). per day) to that of Formodual given as maintenance therapy (1 inhalation twice daily) plus salbutamol as needed, in adult patients with moderate to severe uncontrolled asthma. Results showed that Formodual used as maintenance therapy and therapy as required significantly prolonged the time to onset of the first severe exacerbation (*) compared to Foster used as maintenance therapy plus salbutamol as needed (pPP). The frequency of severe asthma exacerbations per patient / year appeared significantly reduced in the maintenance and reliever therapy compared to the group treated with salbutamol: 0.1476 vs 0, respectively , 2239 (statistically significant reduction: p
Note *: Severe exacerbation is defined as a deterioration of asthma conditions that require hospitalization or emergency treatment, or that requires the use of systemic steroids for more than 3 days.
In another clinical study, a single dose of FORMODUAL 100/6 micrograms induced a rapid bronchodilator effect and rapid relief of dyspnoea symptoms, similar to those obtained with salbutamol 200 micrograms / dose in asthmatic patients when the challenge test is used. with methacholine to induce bronchoconstriction.
COPD
In two 48-week studies in patients with severe COPD (30%
A pivotal study showed a significant improvement in lung function (primary endpoint change in pre-dose FEV1) compared to formoterol after 12 weeks of treatment (adjusted mean difference between Formodual and formoterol: 69 ml), as well as at each clinic visit during the entire treatment period (48 weeks).
The study demonstrated that the mean number of exacerbations per patient / year (exacerbation rate, co-primary endpoint) was statistically significantly reduced with Formodual compared to formoterol treatment (adjusted mean rate 0.80 versus 1.12 in group treated with formoterol, adjusted ratio 0.72, treatment arm) or not with Tiotropium Bromide as concomitant drug.
The other pivotal study, which was a three-arm, randomized, parallel group study conducted in 718 patients, confirmed the superiority of Formodual over formoterol treatment in terms of change in pre-dose FEV1 at the end of treatment. (48 weeks) and demonstrated the non-inferiority of Formodual to the fixed-dose combination budesonide / formoterol for the same parameter.
05.2 "Pharmacokinetic properties -
The systemic exposure to the active substances beclomethasone dipropionate and formoterol, in the fixed combination Formodual, was compared with that of the individual components.
In a pharmacokinetic study conducted in healthy volunteers treated with a single dose of Formodual fixed combination (4 puffs of 100/6 mcg) or a single dose of beclomethasone dipropionate CFC (4 puffs of 250 mcg) and Formoterol HFA (4 puffs of 6 mcg), the AUC of the major active metabolite of beclomethasone dipropionate (beclomethasone-17-monopropionate) and its maximum plasma concentration were 35% and 19% lower, respectively, after administration of the fixed combination, compared to the formulation non extra fine CFC beclomethasone dipropionate, unlike the absorption rate which is faster (0.5 vs 2 hours) with the fixed association compared to beclometasone dipropionate in non extra fine CFC formulation alone.
For formoterol, the maximum plasma concentration was similar after administration of the fixed combination or the extemporaneous combination and systemic absorption is slightly higher after administration of Formodual compared to the extemporaneous combination.
There is no evidence of a pharmacokinetic or pharmacodynamic (systemic) interaction between beclomethasone dipropionate and formoterol.
In a study conducted on healthy volunteers, the use of the AeroChamber Plus spacer device increased the pulmonary distribution of the active metabolite of beclomethasone dipropionate, beclomethasone 17 monopropionate and formoterol by 41% and 45%, respectively, compared to the use of the regulator. Total systemic exposure was unchanged for formoterol, reduced by 10% for beclomethasone 17-monopropionate and increased for unchanged beclomethasone dipropionate.
A lung deposition study conducted in stable COPD patients, healthy volunteers and asthmatic patients showed that on average 33% of the nominal dose is deposited in the lungs of COPD patients compared to 34% of healthy subjects and 31% of patients asthmatics. The plasma exposure levels for beclomethasone 17-monopropionate and formoterol were comparable in the three groups over the 24 hours following inhalation. The total exposure to beclomethasone dipropionate was higher in COPD patients than the exposure observed in patients. asthmatics and in healthy volunteers.
Beclomethasone dipropionate
Beclomethasone dipropionate is a prodrug with a weak binding affinity to the glucocorticoid receptor, which is hydrolyzed by the esterases to the active metabolite beclomethasone-17-monopropionate, which has a more potent topical anti-inflammatory activity than the prodrug beclomethasone dipropionate.
Absorption, distribution and biotransformation
Inhaled beclomethasone dipropionate is rapidly absorbed through the lungs; before absorption it is extensively transformed into its active metabolite, beclomethasone-17-monopropionate, by esterases found in several tissues. The systemic availability of the active metabolite originates from the lungs (36%) and from the gastrointestinal absorption of the dose swallowed. The bioavailability of swallowed beclomethasone dipropionate is negligible, however, pre-systemic conversion to beclomethasone-17-monopropionate results in 41% absorption as an active metabolite.
As the inhaled dose increases, systemic exposure increases approximately linearly. The absolute bioavailability for inhalation is approximately 2% and 62% of the nominal dose for unmodified beclomethasone dipropionate and beclomethasone-17-monopropionate, respectively.
Following intravenous administration, the distribution of beclomethasone dipropionate and its active metabolite is characterized by a high plasma clearance (150 and 120L / hour, respectively), with a small steady state volume of distribution for beclomethasone dipropionate (20L) and a more extensive tissue distribution for its active metabolite (424L).
Plasma protein binding is moderately high.
Elimination
Faecal excretion is the major route of elimination of beclometasone dipropionate, essentially as polar metabolites. Renal excretion of beclometasone dipropionate and its metabolites is negligible. The terminal elimination half-lives are 0.5 hours and 2.7 hours for beclomethasone dipropionate and beclomethasone-17-monopropionate, respectively.
Special populations
The pharmacokinetics of beclomethasone dipropionate in patients with renal and hepatic impairment have not been studied, however since beclomethasone dipropionate undergoes rapid metabolism by esterases present in intestinal fluid, serum, lungs and liver, to give origin of the more polar products beclomethasone-21-monopropionate, beclomethasone-17-monopropionate and beclomethasone, the pharmacokinetics and safety profile of beclomethasone dipropionate should not be modified by hepatic impairment.
Since neither beclomethasone dipropionate nor its metabolites were detected in the urine, an increase in systemic exposure is not expected in patients with impaired renal function.
Formoterol
Absorption and distribution
After inhalation, formoterol is absorbed from both the lungs and the gastrointestinal tract.
The fraction of the inhaled dose that is swallowed following administration with a metered dose inhaler (MDI) can vary between 60% and 90%.
At least 65% of the swallowed dose is absorbed from the gastrointestinal tract. The peak plasma concentration of the unchanged drug is reached between 0.5 and 1 hour after oral administration. Plasma protein binding of formoterol is 61-64% with 34% albumin binding.
There is no binding saturation in the concentration values reached at therapeutic doses. The calculated elimination half-life after oral administration is 2-3 hours.
The absorption of formoterol following inhalation of doses of 12 to 96 mcg of formoterol fumarate is linear.
Biotransformation
Formoterol is extensively metabolised, mainly by direct conjugation of the phenolic hydroxyl group. The conjugate with glucuronic acid is inactive.
The second major route involves O-demethylation followed by conjugation of the phenolic 2-hydroxyl group. The cytochrome P450 isoenzymes CYP2D6, CYP2C19 and CYP2C9 are involved in the O-demethylation of formoterol. The liver is the primary site of metabolism. Formoterol does not inhibit CYP450 enzymes at therapeutically relevant concentrations.
Elimination
The cumulative urinary excretion of formoterol following a single inhalation from a powder inhaler increases linearly over the dose range from 12 to 96 mcg. On average, 8% to 25% of the dose is excreted as unchanged formoterol and total formoterol, respectively. Based on plasma concentrations measured following inhalation of a single dose of 120 micrograms in 12 healthy volunteers, the mean terminal elimination half-life was 10 hours. The enantiomers (RR) and (SS) represent approximately 40% and 60% of the unchanged drug excreted in the urine, respectively. The relative ratio of the two enantiomers remains constant at the doses studied, and no relative accumulation of a enantiomer with respect to the other after repeated dose. After oral administration (40 to 80 micrograms), in healthy volunteers, 6% to 10% of the dose was recovered in the urine as unchanged drug; up to 8% of the dose was recovered in the form of glucuronide.
67% of the oral dose of formoterol is excreted in the urine (mainly as metabolites) and the remainder in the faeces. Renal clearance of formoterol is 150 ml / min.
Special populations
Hepatic / renal impairment: The pharmacokinetics of formoterol have not been studied in patients with hepatic or renal impairment, however, as formoterol is eliminated primarily by hepatic metabolism, increased exposure can be expected in patients with severe hepatic cirrhosis.
05.3 Preclinical safety data -
In animal studies treated with beclomethasone dipropionate and formoterol, in combination or separately, toxicity was observed mainly associated with an exaggerated pharmacological activity. These effects are related to the immuno-suppressive activity of beclomethasone dipropionate and the well-known cardiovascular effects. of formoterol, mainly evident in dogs. There were no increases in toxicity or unexpected results with the administration of the combination.
Reproduction studies in rats have shown dose-dependent effects.
The combination has been associated with reduced female fertility and embryo-fetal toxicity. High dosages of corticosteroids in pregnant animals cause abnormalities of fetal development, including cleft palate and intra-uterine growth retardation, and it is likely that the effects seen with the beclomethasone dipropionate / formoterol combination are due to beclomethasone dipropionate. These effects have only been seen. to a high systemic exposure to the active metabolite beclomethasone-17-monopropionate (200 times the plasma levels expected in patients). In addition, an increase in the duration of gestation and parturition has been shown in animal studies, an effect attributable to the well-known tocolytic action of beta2-sympathomimetics These effects were noted when the levels of formoterol in maternal plasma were below those expected in patients treated with Formodual.
Genotoxicity studies conducted with the beclomethasone dipropionate / formoterol combination do not indicate a mutagenic potential. No carcinogenicity studies have been performed on the proposed combination. However, in animals the known data for the individual components do not suggest potential risks of carcinogenicity in humans.
Preclinical data on CFC-free propellant HFA-134a reveal no special hazard for humans based on conventional studies on safety pharmacology, repeated toxicity, genotoxicity, carcinogenic potential and reproductive toxicity.
06.0 PHARMACEUTICAL INFORMATION -
06.1 Excipients -
Norflurane (HFA-134a), anhydrous ethanol, hydrochloric acid.
06.2 Incompatibility "-
Not relevant.
06.3 Period of validity "-
20 months.
06.4 Special precautions for storage -
Before dispensing to the patient:
Store in a refrigerator (2 - 8 ° C) (for up to 15 months).
After the dispensation:
Do not store at temperatures above 25 ° C (for up to 5 months).
The container contains a pressurized liquid. Do not expose to temperatures higher than 50 ° C. Do not puncture the container.
06.5 Nature of the immediate packaging and contents of the package -
The inhalation solution is contained in a pressurized aluminum container sealed with a metering valve, inserted in a polypropylene dispenser, which incorporates a mouthpiece and is provided with a protective plastic cap.
Each pack contains:
a pressurized container of 120 puffs or a pressurized container of 180 puffs
Not all pack sizes may be marketed.
06.6 Instructions for use and handling -
For pharmacies:
Enter the date of dispensing to the patient on the package.
Make sure there is a period of at least 5 months between the dispensing date to the patient and the expiration date printed on the package.
07.0 HOLDER OF THE "MARKETING AUTHORIZATION" -
Promedica S.r.l.
Via Palermo 26 / A
43122 Parma
Italy
Dealer for sale:
Chiesi Farmaceutici S.p.A., Via Palermo, 26 / A - Parma
08.0 MARKETING AUTHORIZATION NUMBER -
FORMODUAL 100/6 mcg per dispensing pressurized solution for inhalation - 120 puffs
AIC N. 037778014
FORMODUAL 100/6 mcg per dispensing pressurized solution for inhalation - 180 puffs
AIC N. 037778026
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION -
21/09/2007
10.0 DATE OF REVISION OF THE TEXT -
September 2016
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