Active ingredients: Salmeterol, / Fluticasone (fluticasone propionate)
Seretide 25 micrograms / 50 micrograms / dose pressurized inhalation suspension
Seretide 25 micrograms / 125 micrograms / dose pressurized inhalation suspension
Seretide 25 micrograms / 250 micrograms / dose pressurized inhalation suspension
Why is Seretide used? What is it for?
Seretide contains two medicines, salmeterol and fluticasone propionate.
- Salmeterol is a long-acting bronchodilator. Bronchodilators help the airways in the lungs stay clear. This makes it easier for air to get in and out. The effects last for at least 12 hours.
- Fluticasone propionate is a corticosteroid that reduces swelling and irritation in the lungs.
The doctor has prescribed this medicine to help prevent breathing problems such as asthma.
You must use Seretide every day as prescribed by your doctor. This ensures that the medicine works properly to control asthma.
Seretide helps to block the onset of shortness of breath and wheezing. However Seretide should not be used to treat a sudden attack of shortness of breath or wheezing. If this occurs you should use a ready-to-use medicine (" rescue "), fast-acting rescue medicine such as salbutamol. You should always have your fast-acting rescue medicine with you.
Contraindications When Seretide should not be used
Do not use Seretide:
if you are allergic to salmeterol, fluticasone propionate or the other excipient norflurane (HFA 134a).
Precautions for use What you need to know before taking Seretide
Talk to your doctor before taking Seretide if you have:
- Heart disease, including an irregular or fast heartbeat
- Hyperactivity of the thyroid gland
- High blood pressure
- Diabetes mellitus (Seretide may raise the blood sugar level)
- Low levels of potassium in the blood
- Tuberculosis (TB) now or in the past, or other lung infections.
Interactions Which drugs or foods may change the effect of Seretide
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. These include medicines for asthma or any medicines obtained without a prescription. This is because it may not be appropriate to take Seretide with some other medicines.
Tell your doctor if you are taking the following medicines before you start using Seretide:
- blockers (such as atenolol, propranolol and sotalol). Blockers are mainly used to treat high blood pressure or other heart conditions.
- Medicines to treat infections (such as ritonavir, ketoconazole, itraconazole and erythromycin). Some of these medicines can increase the amount of fluticasone propionate or salmeterol in the body. This may increase the risk of getting side effects with Seretide, including irregular heartbeats or make side effects worse.
- Corticosteroids (by mouth or by injection). If you have taken any of these medicines recently, this may increase the risk of this medicine interfering with the adrenal gland.
- Diuretics, used to treat high blood pressure.
- Other bronchodilators (such as salbutamol).
- Medicines based on xanthines. These are often used for the treatment of asthma.
Warnings It is important to know that:
Pregnancy and breastfeeding
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before using this medicine.
Driving and using machines
Seretide is unlikely to affect your ability to drive or use machines.
For those who carry out sporting activities
The use of the drug without therapeutic necessity constitutes doping and can in any case determine positive anti-doping tests.
Dose, Method and Time of Administration How to use Seretide: Posology
Always use this medicine exactly as your doctor or pharmacist has told you. If in doubt, consult your doctor or pharmacist.
- Use Seretide every day until your doctor tells you to stop. Do not exceed the recommended dose. If in doubt, consult your doctor or pharmacist.
- Do not stop using Seretide or reduce your dose of Seretide without first checking with your doctor.
- Seretide is to be inhaled into the lungs through the mouth.
Adults and adolescents 12 years of age and older
- Seretide 25/50 - 2 inhalations twice a day
- Seretide 25/125 - 2 inhalations twice a day
- Seretide 25/250 - 2 inhalations twice a day
Children from 4 to 12 years of age
- Seretide 25/50 - 2 inhalations twice a day
- Seretide is not recommended for use in children less than 4 years of age.
Symptoms can be well controlled by using Seretide twice a day. In this case, the doctor may decide to reduce the dose to once a day. The dose can be changed to:
- once in the evening if you suffer from nocturnal symptoms,
- once in the morning if you suffer from daytime symptoms.
It is very important to follow your doctor's prescription regarding the number of puffs to be given and how often to take the medicine.
If you are using Seretide for asthma, your doctor will check your symptoms regularly.
If your asthma or breathing gets worse, tell your doctor immediately. You may notice that your breathing becomes more labored, that you feel a tightness in your chest more often, or that you need to use your medicine more for quick relief of symptoms. If any of these conditions occur, you should continue to take Seretide but do not increase the number of doses you take. Your respiratory condition could worsen to become particularly severe. Consult your doctor as you may need additional therapy.
Instructions for Use
- Your doctor, nurse or pharmacist will show you how to use the inhaler. They should check how you use the inhaler from time to time. If Seretide is not used properly or as prescribed, this may mean that it will not treat your asthma as it should.
- The medicine is contained in a pressurized can placed inside a plastic liner fitted with a mouthpiece.
- The can is connected to a counter on the back which shows the number of drug doses remaining. Each time the can is pressed, a puff of medicine is released and the counter drops by one dose.
- Be careful not to drop the inhaler as this can decrease the number of doses reported by the counter.
Check the functioning of the inhaler
- Before using the inhaler for the first time, check that it works. Remove the mouthpiece cover by gently pressing the sides of the cover with your thumb and forefinger and pull it out.
- To make sure it works, shake the inhaler well, point the mouthpiece away from you, then press the canister and puff into the air. Repeat this by shaking the inhaler before releasing each puff, until the dose counter shows 120. If you have not used your inhaler for a week or more, release two puffs of the medicine into the air. Using the inhaler It is important to start inhaling as slowly as possible immediately before using the inhaler. 1. Stand or sit upright while using your inhaler. 2. Remove the mouthpiece cover (as shown in the first figure). Check inside and outside to make sure the mouthpiece is clean and free of loose bodies.
- Shake the inhaler 4 or 5 times to make sure that any loose bodies that may be present have been removed and that the contents of the inhaler are evenly mixed.
- Hold the inhaler upright with your thumb on the base, under the mouthpiece. Breathe out as much as possible.
- Place the mouthpiece in your mouth between your teeth. Close your lips around you. Don't bite the mouthpiece.
- Breathe in through your mouth slowly and deeply. Immediately after starting to inhale, press firmly on the top of the can to release a squirt of the medicine. In the meantime, keep inhaling constantly and deeply.
- Hold your breath, take the inhaler out of your mouth and stop pressing your finger on the top of the inhaler. Continue to hold your breath for a few seconds or as long as possible.
- Wait about half a minute between taking each spray and then repeat steps 3 to 7.
- Then rinse your mouth with water and spit it out, and / or brush your teeth. This can help prevent candidiasis (thrush) and hoarseness from occurring.
- After use, always replace the mouthpiece cover immediately to prevent dust from entering. You will hear a click when the mouthpiece protective cap is positioned correctly. If you do not hear the click, turn the mouthpiece cover the other way and try again. Do not use too much force.
Do not rush through steps 4, 5, 6 and 7. It is important that you breathe in as slowly as possible just before using the inhaler. The first few times you should use the inhaler while standing in front of a mirror. If you notice a leak of product, which appears as a "mist", coming from the top of the inhaler or to the sides of your mouth, you should start again from step 3.
As with all inhalers, people caring for children who have been prescribed Seretide Diskus should ensure that they are using the correct inhalation technique, as described above.
If you or your child find it difficult to use the pressurized inhaler, both your doctor and a nurse or other healthcare professional may advise you to use a spacer such as the Volumatic or Aerochamber Plus in conjunction with the inhaler. Your doctor, nurse, pharmacist or other healthcare professional should show you how to use the spacer with the inhaler and how to care for the spacer and answer any questions you may have. It is important that if you use a spacer with the inhaler you do not stop using it without talking to your doctor or nurse first. It is also important that you do not change the type of spacer you are using without talking to your doctor. If you stop using a spacer or change the type of spacer you are using the dose of medicine needed to control asthma may need to be changed.
Always talk to your doctor before making any changes to your asthma treatment.
Older children or people with weak hands may find it easier to hold the inhaler with both hands. Place your two index fingers on the top of the inhaler and both thumbs on the bottom under the mouthpiece.
Get a new pack of medicine when the dose counter shows the number 020. Stop using the inhaler when the counter shows the number 000 as some puffs left in the can may not be enough to give you a full dose. Do not try never alter the number of doses shown on the counter or detach the counter from the can.
Cleaning the inhaler
To prevent blockage of the inhaler, it is important to clean it at least once a week.
To clean the inhaler:
- Remove the protective cap from the mouthpiece.
- Do not remove the metal canister from the plastic inhaler under any circumstances.
- Clean the inside and outside of the mouthpiece and plastic inhaler with a dry cloth or tissue.
- Put the protective cap back on the mouthpiece. You will hear a click when the lid is positioned correctly. If you do not hear the click, turn the mouthpiece cover the other way and try again. Do not use too much force.
Do not put the metal container in water.
Overdose What to do if you have taken too much Seretide
If you use more Seretide than you should
It is important to use the inhaler as directed. If you accidentally take more than the recommended dose, please tell your doctor or pharmacist. You may notice an increase in your heart rate and a feeling of trembling. You may also experience dizziness, headache. , muscle weakness and joint pain.
If you have been using higher doses for a long time, you should consult your doctor or pharmacist. This is because higher doses of Seretide can reduce the amount of steroid hormones produced by the adrenal gland.
If you forget to use Seretide
Do not take a double dose to make up for a forgotten dose. Just take your next dose at the usual time.
If you stop taking Seretide
It is very important that you take Seretide every day as prescribed by your doctor. Keep taking it, until your doctor tells you to stop the treatment. Do not stop or abruptly reduce your dose of Seretide. This may cause your breathing to get worse.
Also, if you stop or abruptly reduce your dose of Seretide this can (very rarely) cause problems with your adrenal glands (adrenal insufficiency) which can sometimes cause side effects.
These side effects can include any of the following:
- Stomach pain
- Tiredness and loss of appetite, feeling unwell
- Nausea and diarrhea
- Weight loss
- Headache or sleepiness
- Lowering of blood sugar levels
- Lowering of blood pressure and fits (convulsions)
When the body is under stress from fever, trauma (such as after a car accident), infection, surgery, adrenal insufficiency can worsen and one of the side effects listed above can occur.
If any of the side effects occur, please contact your doctor or pharmacist. To prevent these symptoms from occurring, your doctor may prescribe you to take extra doses of corticosteroids in tablet form (such as prednisolone).
If you have any further questions on the use of this medicine, ask your doctor, nurse or pharmacist.
Side Effects What are the side effects of Seretide
Like all medicines, this medicine can cause side effects, although not everybody gets them. To reduce the chance of side effects, your doctor will prescribe the lowest dose of Seretide needed to control your asthma.
Allergic reactions: You may notice that your breathing suddenly worsens immediately after taking Seretide. You may feel very short of breath and cough. You may also notice itching, rash (hives) and swelling (usually of the face, lips, tongue or throat), or you may suddenly feel that your heart is beating very fast or feel faint and light-headed (which can cause you to collapse or lose consciousness). suddenly occur after using Seretide, stop using Seretide and tell your doctor immediately. Allergic reactions to Seretide are uncommon (affecting less than 1 in 100 people).
Other side effects are listed below:
Very common (affects more than 1 in 10 people)
- Headache, which usually improves with continued therapy.
- An increase in the number of colds has been reported in patients with chronic obstructive pulmonary disease (COPD)
Common (affecting less than 1 in 10 people)
- Thrush (painful, creamy-yellow, raised patches) in the mouth and throat. Also, tongue tenderness, hoarseness and throat irritation. Rinsing your mouth with water and spitting it out immediately and / or brushing your teeth after each dose may help. Your doctor may prescribe an antifungal to treat thrush.
- Pain, joint swelling and muscle pain.
- Muscle cramps
The following side effects have also been reported in patients with chronic obstructive pulmonary disease (COPD):
- Pneumonia and bronchitis (lung infection). Tell your doctor if you notice any of the following symptoms: increased sputum production, change in sputum color, fever, chills, increased cough, increased breathing problems.
- Bruises and fractures
- Sinus inflammation (a feeling of tightness or fullness in the nose, cheeks and behind the eyes, sometimes accompanied by throbbing pain)
- Reduction of potassium content in the blood (irregular heartbeat, muscle weakness, cramps may be observed)
Uncommon (affects less than 1 in 100 people)
- Increased sugar (glucose) content in the blood (hyperglycaemia). If you have diabetes, more frequent blood glucose monitoring and possibly adjustment of diabetes therapy may be necessary.
- Cataract (clouding of the lens of the eye).
- Very fast heart beat (tachycardia).
- Feeling of shaking (tremor) and fast or irregular heartbeat (palpitations) - these side effects are usually harmless and lessen with continued therapy.
- Chest pain.
- Feeling of concern (these effects are particularly common in children).
- Disturbed sleep.
- Allergic skin rash.
Rare (affects less than 1 in 1000 people)
- Difficulty in breathing or wheezing that gets worse immediately after taking Seretide. If this happens, stop using your Seretide inhaler immediately. Use your fast-acting medicine to help your breathing and tell your doctor immediately.
- Seretide can alter the normal production of steroid hormones in the body, particularly if you have taken high doses over a prolonged period of time. Effects include: - Growth slowdown in children and adolescents - Thinning of bones - Glaucoma - Weight gain - Rounded (moon-shaped) appearance of the face (Cushing's Syndrome) Your doctor will check you regularly for any of these side effects and will make sure you take the lowest dose of Seretide to control your asthma.
- Behavioral changes, such as unusual hyperactivity and irritability (these effects occur particularly in children).
- Irregular heartbeat or having extra heartbeats (arrhythmia). Tell your doctor but do not stop taking Seretide unless your doctor tells you to stop taking the medicine.
- A "fungal infection in the esophagus (throat)" which could cause difficulty in swallowing.
Frequency not known, but can occur
- Depression or aggression. These effects are more likely to occur in children.
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 Seretide Pressurized suspension after the expiry date which is stated on the label and carton after EXP. The expiry date refers to the last day of the month.
- Do not store above 25 ° C.
- Do not store Seretide in a cold place as it may not work well.
- The container contains a pressurized liquid. Do not expose to temperatures above 50 ° C, protect from direct sunlight. Do not puncture or burn the container, even when it is empty.
- As with most inhaled medicinal products in pressurized containers, the therapeutic effect of this medicinal product may diminish when the container is cold.
Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Composition and pharmaceutical form
What Seretide contains
- Each dose (delivered by the metering valve) contains 25 micrograms of salmeterol (as salmeterol xinafoate) and 50, 125 or 250 micrograms of fluticasone propionate.
- The other excipient is the propellant: norflurane (HFA 134a)
What Seretide looks like and contents of the pack
- Seretide is supplied in a metered-dose inhaler that delivers the medicine as a pressurized suspension for inhalation into the lungs through the mouth.
- The pressurized container contains a white to off-white suspension for inhalation.
- The containers are placed in a plastic bag that incorporates a mouthpiece and are filled with powder capsules.
- The inhalers are packaged in cardboard boxes containing 1, 3 or 10 inhalers.
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
SERETIDE
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each Seretide delivery provides:
25 mcg of salmeterol (as salmeterol xinafoate) and 50, 125 or 250 mcg of fluticasone propionate (delivered by the metering valve). This is equivalent to 21 mcg of salmeterol and 44, 110 or 220 mcg of fluticasone propionate delivered from the inhaler (delivered dose).
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Pressurized suspension for inhalation
The container contains a white to off-white suspension.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Seretide is indicated for the regular treatment of asthma when the use of a combination medicinal product (long-acting beta-2 agonist and inhaled corticosteroid) is appropriate:
- in patients who are not adequately controlled on inhaled corticosteroids and "as needed" short-acting beta-2-agonists
or
- in patients who are already adequately controlled on both inhaled corticosteroids and long-acting beta-2-agonists
04.2 Posology and method of administration
Seretide is for inhalation use only.
Patients should be advised that taking Seretide therapy daily, in order to derive the best benefit, is necessary even when they have no symptoms.
Patients should be checked regularly by a doctor to ensure that the dosage of Seretide remains optimal and is only changed on medical advice. The dose should correspond to the lowest dose at which effective symptom control is maintained. When symptom control is maintained with the lowest strength of the combination given twice daily, then the next step may involve administering the inhaled corticosteroid alone as a trial. Alternatively, patients requiring long-acting beta-2-agonist therapy may be switched to once-daily Seretide if, in the physician's judgment, this constitutes adequate therapy to maintain disease control. Once daily administration should be done in the evening if the patient has a history of nocturnal symptoms and in the morning if the patient has a history of predominantly daytime symptoms.
Patients should be prescribed the dose of Seretide containing the dose of fluticasone propionate appropriate for the severity of the disease. Note: The dosage of Seretide 25 mcg / 50 mcg is not appropriate for the treatment of severe asthma in children and adults. The prescribing physician should be aware that, in patients with asthma, fluticasone propionate is as effective as other steroids. inhalers at a daily dose equal to about half that of the latter. For example, 100 mcg of fluticasone propionate is approximately equivalent to 200 mcg of beclomethasone dipropionate (in formulation with CFC) or budesonide.
If a patient needs to administer dosages other than those recommended, appropriate doses of beta agonist and / or corticosteroid should be administered.
Recommended doses
Adults and adolescents 12 years of age and older:
Two inhalations of 25 mcg of salmeterol and 50 mcg of fluticasone propionate twice daily.
or
Two inhalations of 25 mcg of salmeterol and 125 mcg of fluticasone propionate twice daily.
or
Two inhalations of 25 mcg of salmeterol and 250 mcg of fluticasone propionate twice daily.
In adults or adolescents with moderate persistent asthma (defined as patients with daily symptoms, daily use of reliever medication and moderate to severe respiratory limitation) for whom rapid achievement of asthma control is essential, it can be considered. Consider initial maintenance therapy with Seretide for a short trial period. In such cases, the recommended starting dose is two inhalations of 25 micrograms of salmeterol and 50 micrograms of fluticasone propionate twice daily. asthma, treatment should be re-evaluated and the option of switching to inhaled corticosteroid alone should be considered. Regular follow-up of the patient after a transition to inhaled corticosteroid therapy is important.
There has been no clear benefit compared to inhaled fluticasone propionate alone, used as initial maintenance therapy, when one or two of the severity criteria described above are not met. In general, inhaled corticosteroid therapy remains the first-line treatment for most patients. Seretide is not indicated for the initial treatment of mild asthma. The dosage of Seretide 25 mcg / 50 mcg is not appropriate in adults and children with severe asthma; in patients with severe asthma it is recommended that the appropriate dosage of inhaled corticosteroid be established prior to use any fixed association.
Children aged 4 years or older
Two inhalations of 25 mcg of salmeterol and 50 mcg of fluticasone propionate twice daily.
In children, the maximum authorized dose of fluticasone propionate administered by Seretide pressurized inhalation suspension is 100 micrograms twice daily.
There are no data available on the use of Seretide pressurized inhalation suspension in children less than 4 years of age.
Children under the age of 12 may have difficulty synchronizing use of the aerosol dispenser with inspiration. The use of a spacer device with Seretide pressurized inhalation suspension is recommended in patients who have or are likely to have difficulty in coordinating use of the regulator with inspiration. A recent clinical study showed that pediatric patients using the spacer device achieved similar exposure to adults who did not use the spacer device and pediatric patients who used the spacer device. they used Seretide diskus; this confirms that the spacer devices compensate for the inadequate inhalation technique (see paragraph 5.2).
Volumatic or Aerochamber Plus spacer devices (according to national recommendations) can be used. There are limited data available demonstrating an increase in systemic exposure when the Aerochamber Plus spacer device is used compared to the Volumatic device (see section 4.4).
Patients should receive "appropriate instruction in the proper use and maintenance of their inhaler and spacer;" in addition, their inhalation technique must be controlled to ensure optimal distribution of the inhaled drug to the lungs. Patients should continue to use the same type of spacer device as switching from one spacer device to another may result in changes in the dose delivered to the lungs (see section 4.4).
The minimum effective dose should always be re-evaluated when one inhaler device is introduced into use or another is adopted.
Special patient groups:
No dose adjustment is necessary in elderly patients or in patients with impaired renal function. There are no data available on the use of Seretide in patients with impaired hepatic function.
Instructions for Use:
Patients should be given adequate instructions for appropriate use of the inhaler (see Patient Information Leaflet).
During inhalation, the patient should preferably be in an upright or sitting position. The inhaler has been designed for use in an upright position.
Check the functioning of the inhaler:
Before using the inhaler for the first time, remove the protective cap from the mouthpiece by squeezing it slightly at the sides, shake the inhaler well, hold the inhaler between your fingers and thumb with the thumb at the base, under the mouthpiece, then spray in the air until the counter shows the number 120, to make sure it works. The inhaler should be shaken immediately before each puff. If the inhaler has not been used for a week or more, remove the protective cap from the mouthpiece, shake the inhaler well and make two puffs in the air. Each time the inhaler is activated the dose counter will decrease by one.
Using the inhaler:
1. The patient should remove the mouthpiece cover by gently pressing the sides of the cover.
2. The patient should check the inside and outside of the inhaler, including the mouthpiece, for any loose bodies.
3. The patient should shake the inhaler well to ensure that any loose bodies are removed and that the contents of the inhaler are mixed evenly.
4. The patient should hold the inhaler upright between the thumb and forefinger (the thumb should rest on the base of the inhaler, under the mouthpiece).
5. The patient should exhale as much as possible and place the mouthpiece in the mouth between the teeth and close the lips around them. The patient must be instructed not to bite the mouthpiece.
6. Immediately after starting to inhale through the mouth, the patient should firmly press the top of the inhaler to release Seretide while continuing to inhale constantly and deeply.
7. While holding their breath, the patient should take the inhaler out of his mouth and lift his finger from the top of the inhaler. The patient should continue to hold their breath for as long as possible.
8. To take a second inhalation, the patient must hold the inhaler upright and must wait about half a minute before repeating steps 3 to 7.
9. The patient should immediately return the mouthpiece cover to the correct position by pressing firmly and snapping it open. No excessive pressure is required, and the lid will snap into place.
IMPORTANT
The patient should not rush through steps 5, 6 and 7. It is important that the patient begins to inhale as slowly as possible immediately before pressing the inhaler. For the first few times the patient should practice in front of a mirror. If you notice a "mist" coming from the top or sides of the inhaler you should repeat the operation starting from step 2.
The patient must obtain a new pack of medicine when the dose counter shows the number 020. The counter will stop at 000 when all the expected doses have been used. Replace the inhaler when the dose counter shows the number 000.
Never try to alter the number of doses shown on the counter or to detach the counter from the metal container.
The counter cannot be adjusted and is attached to the container.
Cleaning the inhaler:
The inhaler should be cleaned at least once a week.
1. Remove the protective cap from the mouthpiece.
2. Do not remove the container from the plastic inhaler.
3. Dry the inside and outside of the mouthpiece and plastic inhaler with a dry cloth or tissue.
4. Put the protective cap back on the mouthpiece in the correct position. No excessive pressure is required, and the lid will snap into place.
DO NOT IMMERSE THE METAL CONTAINER IN WATER
04.3 Contraindications
Seretide is contraindicated in patients with hypersensitivity to one of the active substances or to the excipient.
04.4 Special warnings and appropriate precautions for use
Seretide should not be used to treat symptoms of acute asthma for which a rapid onset, short-acting bronchodilator is required. Patients should be advised to always have their medicine available for use in the resolution of an acute asthma attack.
Patients should not start Seretide therapy during an asthma flare-up episode or if they have significantly worsening or acute worsening of asthma.
Asthma-related serious adverse events and flare-ups may occur during treatment with Seretide. Patients should be advised to continue treatment but should be advised to seek medical attention if asthma symptoms remain uncontrolled or worsen afterwards. the initiation of Seretide therapy.
Increased use of short-acting bronchodilators for the relief of asthma symptoms indicates worsening asthma control and patients should be under medical supervision.
Sudden and progressive worsening of asthma control is potentially life-threatening and the patient should be urgently seen by a physician. Consideration should be given to increasing corticosteroid therapy.
Once asthma symptoms are controlled, consideration may be given to gradually reducing the dose of Seretide. It is important to check patients regularly from the time the treatment dose is reduced. The lowest effective dose of Seretide should be used (see section 4.2).
Seretide treatment should not be stopped abruptly.
As with all inhaled corticosteroid medications, Seretide should be administered with caution to patients with pulmonary tuberculosis.
Rarely, Seretide may cause cardiac arrhythmias such as supraventricular tachycardia, extrasystoles and atrial fibrillation at high therapeutic doses, and a transient mild decrease in serum potassium. Therefore Seretide should be used with caution in patients with severe cardiovascular disease, heart rhythm abnormalities, diabetes mellitus, thyrotoxicosis, uncorrected hypokalaemia or patients predisposed to have low serum potassium levels.
There have been very rare reports of increases in blood glucose levels (see section 4.8) and this should be taken into consideration when prescribing Seretide to patients with a history of diabetes mellitus.
As with other inhalation therapies paradoxical bronchospasm may occur with an immediate increase in wheezing after dosing. Seretide therapy should be discontinued immediately, the patient's condition checked and alternative therapy instituted if necessary.
Systemic effects may occur with any inhaled corticosteroid, particularly at high doses prescribed for long periods of time. These effects are much less likely to occur than with oral corticosteroids. Possible systemic effects include: Cushing's syndrome, Cushingoid aspect, adrenal suppression, decreased bone mineral density, cataracts and glaucoma and more rarely a range of psychological and behavioral effects including psychomotor hyperactivity, sleep disturbances, anxiety, depression or aggression ( especially in children). It is therefore important that the patient is monitored regularly and the inhaled corticosteroid dose is reduced to the lowest dose at which effective asthma control is maintained.
Prolonged treatment of patients with high-dose inhaled corticosteroids may result in adrenal suppression and acute adrenal crisis. Very rare cases of adrenal suppression and acute adrenal crisis have also been described with doses of fluticasone propionate between 500 and less than 1,000 mcg. Situations that can potentially trigger an acute adrenal crisis include: trauma, surgery, infection, or any rapid reduction in dosage. Onset symptoms are typically vague and may include: anorexia, abdominal pain, weight loss, fatigue, headache, nausea, vomiting, hypotension, decreased level of consciousness, hypoglycemia, and convulsions. The need for additional systemic corticosteroid coverage during times of stress or in elective surgery should be considered.
Systemic absorption of salmeterol and fluticasone propionate occurs largely through the lungs. potentially at an increased risk of systemic adverse effects.Single dose pharmacokinetic data have shown that systemic exposure to salmeterol and fluticasone propionate can increase up to twice when the Aerochamber Plus spacer device is used with Seretide, compared to when the Volumatic spacer device is used.
The benefits of inhalation therapy with fluticasone propionate should minimize the need for oral corticosteroid therapy, however patients switched from oral steroid therapy may remain at risk of impaired adrenal reserve for a considerable period of time. Patients who have previously required high-dose emergency corticosteroids may also be at risk. This possibility of a residual impairment must always be kept in mind in emergency situations and in those considered capable of producing stress; appropriate corticosteroid therapy should be considered in such cases. The degree of adrenal impairment may require specialist evaluation prior to adopting specific procedures.
Ritonavir can significantly increase the concentration of fluticasone propionate in plasma. Therefore, concomitant use should be avoided unless the potential benefit to the patient outweighs the risk of systemic side effects of corticosteroids. There is also an increased risk of systemic side effects when fluticasone propionate is co-administered with other potent CYP3A inhibitors (see section 4.5).
In a 3-year study in patients with Chronic Obstructive Pulmonary Disease (COPD) receiving Seretide compared to placebo (see section 4.8), there was an increase in reports of lower respiratory tract infections (particularly pneumonia and bronchitis) In a 3-year study in COPD patients, older patients, those with a lower body mass index and patients with a very severe form of the disease (FEV1
Data from a large clinical trial (the Salmeterol Multi-Center Asthma Research Trial, SMART) suggested that African-American patients were at increased risk of serious respiratory events or death when treated with salmeterol compared to placebo. (see section 5.1). It is not known whether this was due to pharmacogenetic or other factors. Patients of black African or Afro-Caribbean descent should be advised to continue treatment but to seek medical attention if asthma symptoms remain uncontrolled or worsen during Seretide therapy.
Simultaneous use of systemic ketoconazole significantly increases systemic exposure to salmeterol. This can lead to an increased incidence of systemic effects (eg prolongation of the QTc interval and palpitations). Concomitant treatment with ketoconazole or other potent CYP3A4 inhibitors should therefore be avoided unless the benefits outweigh the potentially increased risk of systemic side effects for salmeterol treatment (see section 4.5).
Pediatric population
Children and adolescents aged less than 16 years treated with high doses of fluticasone propionate (typically ≥ 1,000 μg / day) may be at particular risk of systemic effects. Systemic effects may occur, particularly at high doses prescribed for long periods of time. Possible systemic effects include: Cushing's syndrome, Cushingoid aspect, adrenal suppression, acute adrenal crisis and growth retardation in children and adolescents and more rarely a range of psychological and behavioral effects including psychomotor hyperactivity, sleep disturbances, anxiety, depression or aggression.
It is recommended that the height of children receiving prolonged inhaled corticosteroid treatment be monitored regularly. The dose of inhaled corticosteroid should be reduced to the lowest dose at which effective asthma control is maintained.
04.5 Interactions with other medicinal products and other forms of interaction
Selective and non-selective beta-blockers should be avoided in patients with asthma unless there are compelling reasons for their use.
The concomitant use of other drugs containing beta-adrenergics can give rise to a potentially additive effect.
Fluticasone propionate
Under normal conditions, low plasma concentrations of fluticasone propionate are achieved following inhaled administration; this is due to the extensive first pass metabolism and high systemic clearance mediated by cytochrome P450 3A4 in the intestine and liver. Therefore, clinically significant interactions mediated by fluticasone propionate are unlikely.
In an interaction study with intranasally administered fluticasone propionate in healthy subjects, ritonavir (a very potent inhibitor of cytochrome P450 3A4) at a dose of 100 mg twice daily increased the plasma concentration of fluticasone several hundred-fold. propionate, resulting in significantly reduced concentrations of serum cortisol. No information on this type of interaction is available for inhaled fluticasone propionate, but a significant increase in plasma levels of fluticasone propionate is expected. Cases of Cushing's syndrome and adrenal suppression have been reported. Concomitant administration should be avoided unless the benefits outweigh the increased risk of systemic side effects of glucocorticoids.
In a small study in healthy volunteers, the slightly less potent CYP3A inhibitor ketoconazole increased fluticasone propionate exposure by 150% after a single inhalation. This resulted in a reduction in plasma cortisol greater than that seen with fluticasone propionate alone. Concomitant treatment with other potent CYP3A inhibitors, such as itraconazole, is also expected to result in an increased systemic exposure to fluticasone propionate and the risk of systemic side effects. long-term treatment with such drugs should be avoided if possible.
Salmeterol
Potent inhibitors of cytochrome CYP3A4
Concomitant administration of ketoconazole (400 mg once daily orally) and salmeterol (50 micrograms twice daily by inhalation) in 15 healthy subjects for 7 days resulted in a significant increase in salmeterol exposure in the plasma (1.4 times the Cmax and 15 times the AUC). This may lead to an increased incidence of other systemic effects from salmeterol treatment (eg QTc interval prolongation and palpitations) compared to treatment with salmeterol alone or ketoconazole alone (see section 4.4).
No clinically significant effects on blood pressure, heart rate, blood glucose and potassium levels were noted. Co-administration with ketoconazole did not increase the elimination half-life of salmeterol or increase the accumulation of salmeterol for repeated doses.
Concomitant administration of ketoconazole should be avoided unless the benefits outweigh the potentially increased risk of systemic side effects for salmeterol treatment. There is likely to be a similar risk of interaction with other potent CYP3A4 inhibitors (e.g. itraconazole, telithromycin, ritonavir).
Moderate inhibitors of cytochrome CYP3A4
Concomitant administration of erythromycin (500 mg three times daily orally) and salmeterol (50 micrograms twice daily by inhalation) in 15 healthy subjects for 6 days resulted in a small but not statistically significant increase in " salmeterol exposure (1.4 times the Cmax and 1.2 times the AUC). Concomitant administration of erythromycin was not associated with any serious adverse effects.
04.6 Pregnancy and lactation
Fertility
There are no human data. However, animal studies have shown that there is no effect of salmeterol and fluticasone propionate on fertility.
Pregnancy
A moderate amount of data on pregnant women (between 300 - 1000 pregnancy outcomes) indicates no malformative or fetal / neonatal toxicity by salmeterol and fluticasone propionate. Studies in animals have shown reproductive toxicity following administration of beta-2 agonists and glucocorticoids (see section 5.3).
Administration of Seretide to pregnant women should only be considered if the expected benefit to the mother is greater than the possible risk to the fetus.
The lowest effective dose of fluticasone propionate needed to maintain adequate asthma control should be used in the treatment of pregnant women.
Pregnancy
It is unknown whether salmeterol and fluticasone propionate / their metabolites are excreted in human milk.
Studies have shown that salmeterol and fluticasone propionate, and their metabolites, are excreted in the milk of lactating rats.
A risk to breastfed newborns / infants cannot be excluded. A decision must be made whether to discontinue breastfeeding or to discontinue Seretide therapy taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.
04.7 Effects on ability to drive and use machines
No studies on the ability to drive and use machines have been performed.
04.8 Undesirable effects
Since Seretide contains salmeterol and fluticasone propionate, the type and severity of adverse reactions associated with each of the two components can be predicted. There is no incidence of additional adverse events following concomitant administration of the two compounds.
Adverse events that have been associated with salmeterol / fluticasone propionate are listed below by system organ class and frequency. Frequencies are defined as: very common (≥1 / 10), common (≥1 / 100, placebo arm was not considered.
1 Commonly reported with placebo
2 Very commonly reported with placebo
3 Reported in a 3-year study in COPD patients
4 See section 4.4
Description of selected adverse reactions
Pharmacological undesirable effects of treatment with beta-2-agonists, such as tremor, palpitations and headache, have been reported and tend to be transient and to decrease with regular therapy.
Due to the fluticasone propionate component, hoarseness and candidiasis (thrush) of the mouth and throat may occur in some patients. Hoarseness and candidiasis can be relieved by gargling with water after using the medicine. Symptomatic candidiasis can be treated with topical antifungal therapy while continuing treatment with Seretide.
Pediatric population
Possible systemic effects include Cushing's syndrome, Cushingoid appearance, adrenal suppression and growth retardation in children and adolescents (see section 4.4). Children may also report anxiety, sleep disturbances and behavioral changes, including hyperactivity and irritability.
04.9 Overdose
No data on overdose with Seretide are available from clinical trials, however the available data on overdose with both drugs taken individually are provided below.
The signs and symptoms of salmeterol overdose are tremor, headache and tachycardia. Preferred antidotes are cardioselective beta-blockers which should be used with caution in patients with a history of bronchospasm. If Seretide therapy has to be discontinued due to overdose of the beta-agonist component of the drug, "appropriate steroid replacement therapy should be considered. Hypokalaemia may also occur and additional administration should be considered. of potassium.
Acute: Acute inhalation of fluticasone propionate in doses higher than those recommended can lead to temporary suppression of adrenal function. This does not require emergency measures as adrenal function is recovered in a few days as demonstrated by measurements of the plasma cortisol.
Chronic overdose of inhaled fluticasone propionate: refer to section 4.4: risk of adrenal suppression. Monitoring of the adrenal reserve may be necessary. In the event of fluticasone propionate overdose, Seretide therapy may be continued at an appropriate dosage for symptom control.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: adrenergics and other antiasthmatics.
ATC code: R03AK06.
Clinical Studies with Seretide in Asthma
A 12-month clinical study (Gaining Optimal Asthma ControL, GOAL), conducted in 3,416 adult and adolescent patients with persistent asthma, compared the safety and efficacy of Seretide to an inhaled corticosteroid (fluticasone propionate) used on its own. in order to verify the achievement of asthma control objectives. Dosage was increased every 12 weeks until ** Total Asthma Control or the highest drug dose in the study was achieved. The GOAL study demonstrated that more patients treated with Seretide achieved asthma control than patients. patients treated with inhaled corticosteroid alone and this control was achieved with a lower dose of corticosteroid.
Good Asthma Control was achieved more rapidly with Seretide than with inhaled corticosteroid alone. The treatment time required for 50% of subjects to achieve their first week of Good Control was 16 days for Seretide compared with 37 days for the Inhaled corticosteroid group In the subgroup of steroid-naive asthma patients the treatment time required to achieve individual Good Control was 16 days for Seretide compared to 23 days for the inhaled corticosteroid group.
The overall results of the study showed:
* Good control of asthma; occasional presence of symptoms or use of SABA or lung function less than 80% of the expected together with the absence of nocturnal awakenings, absence of exacerbations and absence of undesirable effects that require a modification of the therapy.
** Total control of asthma; absence of symptoms, absence of use of SABA, lung function greater than or equal to "80% of" expected, absence of nocturnal awakenings, absence of exacerbations and absence of undesirable effects that require a modification of the therapy.
The results of this study suggest that Seretide 50/100 micrograms twice daily can be considered as initial maintenance therapy in patients with moderate persistent asthma for whom rapid asthma control is considered essential (see section 4.2).
A double-blind, randomized, parallel-group study in 318 patients aged 18 years and over with persistent asthma evaluated the safety and tolerability of administering 2 inhalations of Seretide twice daily (doubling the dose). ) for a period of two weeks. The study showed that doubling of inhalations for each dose of Seretide for up to 14 days results in a small increase in the incidence of beta-agonist-related adverse events (tremor, 1 patient [1%] vs 0; palpitations, 6 patients [3%] vs 1 [muscle cramps, 6 patients [3%] vs 1 [
Salmeterol Multi-Center Asthma Research Trial (SMART)
SMART was a multi-center, randomized, double-blind, placebo-controlled, parallel-group, 28-week study conducted in the US that randomized 13,176 patients to treatment with salmeterol (50 mcg twice daily) and 13,179 patients on placebo, in addition to each patient's normal asthma therapy. Patients were enrolled if they were 12 years of age or older, had asthma, and were using asthma medication at enrollment (but not a Long Acting Beta Agonist, LABA). of study entry, baseline use of inhaled corticosteroids was recorded, although their use was not required in the study. The primary endpoint of the SMART study was the combined number of respiratory deaths and respiratory events that put at risk the life.
Key Findings from SMART Study: Primary Endpoint
(The risk in bold type is statistically significant at the 95% confidence level)
Key Findings from SMART Study for Inhaled Steroid Use at Baseline: Secondary Endpoints
(* = the risk could not be calculated due to the absence of events in the placebo group. The risk in bold type is statistically significant at the 95% confidence interval. The secondary endpoints reported in the table above reached the statistical significance in the whole population.) The combined secondary endpoints of deaths from all causes or life-threatening events, deaths from all causes or hospitalizations from all causes did not reach statistical significance in the whole population.
Mechanism of action:
Seretide contains salmeterol and fluticasone propionate which have different mechanisms of action.
The respective mechanism of action of both drugs is discussed below.
Salmeterol:
Salmeterol is a selective long-acting (12 hours) beta-2-adrenoceptor agonist with a long side chain that binds to the receptor exosite.
Salmeterol produces longer-lasting bronchodilation, of at least 12 hours, than that achieved with the recommended doses of conventional short-acting beta-2-agonists.
Fluticasone propionate:
Fluticasone propionate, administered by inhalation, at recommended doses has glucocorticoid anti-inflammatory activity in the lung, with consequent reduction of symptoms and exacerbations of asthma, with fewer adverse effects than systemic administration of corticosteroids.
05.2 Pharmacokinetic properties
When salmeterol and fluticasone propionate are administered in combination by inhalation, the pharmacokinetics of each are similar to that seen when the drugs are administered separately. Therefore, for the purposes of pharmacokinetic evaluations each of the two components can be considered separately.
Salmeterol:
Salmeterol acts locally in the lung and therefore plasma levels are not indicative of the therapeutic effect. In addition, only limited data are available on the pharmacokinetics of salmeterol due to the technical difficulty of analyzing the drug in plasma caused by low plasma concentrations at therapeutic doses administered to by inhalation (approximately 200 picograms / ml or less).
Fluticasone propionate:
The absolute bioavailability of a single dose of inhaled fluticasone propionate in healthy volunteers ranges from approximately 5 to 11% of the nominal dose depending on the type of inhalation device used. A lower level of systemic exposure to inhaled fluticasone propionate has been observed in asthmatic patients.
Systemic absorption occurs mainly through the lungs and is initially rapid, then prolonged. The remainder of the inhaled dose can be ingested but contributes minimally to systemic exposure due to low aqueous solubility and pre-systemic metabolism, with a oral availability less than 1%. There is a linear increase in systemic exposure in relation to the increase in the inhaled dose.
The distribution of fluticasone propionate is characterized by a "high plasma clearance (1150 mL / min), a large steady-state volume of distribution (approximately 300 L) and a" final half-life of approximately 8 hours.
The plasma protein binding is 91%.
Fluticasone propionate is eliminated very rapidly from the systemic circulation. The major route is metabolism to an inactive carboxylic acid compound by the CYP3A4 enzyme of the cytochrome P450 system. Other unidentified metabolites have been detected in faeces.
Renal clearance of fluticasone propionate is negligible. Less than 5% of the dose is excreted in the urine, mainly as metabolites. The main portion of the dose is excreted with the faeces in the form of metabolites and unchanged drug.
Pediatric population
The effect of treatment for 21 days with Seretide pressurized suspension for inhalation 25/50 mcg (2 inhalations twice a day with or without spacer device) or with Seretide Diskus 50 / 100mcg (1 inhalation twice a day) was evaluated in 31 children aged 4 to 11 years with mild asthma. Systemic exposure of fluticasone propionate was similar for Seretide pressurized inhalation suspension with spacer device (107 pg hr / mL [95% CI: 45.7, 252.2]) and Seretide Diskus (138 pg hr / mL [95% CI: 69.3, 273.2]), but lower for Seretide pressurized inhalation suspension (24 pg hr / mL [95% CI: 9.6, 60.2]). Systemic exposure of salmeterol was similar for Seretide Pressurized Inhalation Suspension, Seretide Pressurized Inhalation Suspension with Spacer Device and Seretide Diskus (126 pg hr / mL [95% CI: 70, 225]), 103 pg hr / mL [ 95% CI: 54, 200], and 110 pg hr / mL [95% CI: 55, 219], respectively).
05.3 Preclinical safety data
In animal studies in which salmeterol xinafoate and fluticasone propionate were administered separately, the only elements of concern to human health were the effects associated with excessive pharmacological actions.
In animal reproduction studies, glucocorticoids have been shown to induce malformations (cleft palate, skeletal malformations). However, these experimental results in animals do not seem to be of relevance to human administration at the recommended doses. Animal studies with salmeterol xinafoate gave rise to embryofoetal toxicity only at high exposure levels. Following concomitant administration in rats, at doses associated with glucocorticoid induction of known abnormalities, an increase in glucocorticoid induction was observed. "incidence of umbilical artery transposition and incomplete ossification of the occipital bone.
The non-chlorofluorocarbon propellant, Norflurane, has been shown, in a "wide range of animal species exposed daily for two-year periods, to have no toxic effects at very high vapor concentrations, far in excess of those to which patients are likely to be exposed."
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Norflurane (HFA134a)
06.2 Incompatibility
Not relevant.
06.3 Period of validity
2 years
06.4 Special precautions for storage
Firmly place the mouthpiece cover back on the mouthpiece and snap it open.
The container contains a pressurized liquid. Do not store above 25 ° C. The container must not be punctured, broken or burned even if apparently empty.
As with most medicines contained in pressurized containers, the therapeutic effect of this medicine may diminish when the container is cold.
06.5 Nature of the immediate packaging and contents of the package
The suspension is contained in an 8 ml pressurized container in aluminum alloy, lacquered inside, sealed with a metering valve. The container is placed in a plastic inhaler equipped with a nebulizer mouthpiece and a protective dust cap. container is connected to a dose counter which shows the number of drug doses remaining. The number is visible in a window on the back of the inhaler in plastic material. A pressurized container delivers 120 doses.
The inhalers are available in cardboard boxes containing:
1 inhaler of 120 doses
or 3 inhalers of 120 doses
or 10 inhalers of 120 doses - use limited to hospital pharmacies (for dispensing purposes).
Not all pack sizes may be marketed.
06.6 Instructions for use and handling
No special instructions
07.0 MARKETING AUTHORIZATION HOLDER
GlaxoSmithKline S.p.A. - Via A. Fleming, 2 - Verona
08.0 MARKETING AUTHORIZATION NUMBER
SERETIDE 25/50 mcg / dose Pressurized suspension for inhalation
- 1 container 120 puffs AIC: 034371106 / M
SERETIDE 25/125 mcg / dose Pressurized suspension for inhalation
- 1 container 120 puffs AIC: 034371118 / M
SERETIDE 25/250 mcg / dose Pressurized suspension for inhalation
- 1 container 120 puffs AIC: 034371120 / M
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
14 May 2001 / May 2010
10.0 DATE OF REVISION OF THE TEXT
July 2013
