When a pharmaceutical company changes an SPC or PIL, a new version is published on medicines.ie. For each version, we show the dates it was published on medicines.ie and the reasons for change.
4.5 Interaction with other medicinal products and other forms of interaction
Beta-adrenergic blockers may weaken or antagonise the effect of salmeterol. Both non-selective and selective beta-blockers should be avoided unless there are compelling reasons for their use.
………………..etc
Moderate CYP 3A4 inhibitors Co-administration of erythromycin (500mg orally three times a day) and salmeterol (50µg inhaled twice daily) in 15 healthy subjects for 6 days resulted in a small but non-statistically significant increase in salmeterol exposure (Cmax mean ratio was 1.40) (1.4-fold Cmax and 1.2-fold AUC). Co-administration with erythromycin was not associated with any serious adverse effects.
Moderate CYP 3A4 inhibitors
Co-administration of erythromycin (500mg orally three times a day) and salmeterol (50µg inhaled twice daily) in 15 healthy subjects for 6 days resulted in a small but non-statistically significant increase in salmeterol exposure (Cmax mean ratio was 1.40) (1.4-fold Cmax and 1.2-fold AUC). Co-administration with erythromycin was not associated with any serious adverse effects.
SUMMARY OF PRODUCT CHARACTERISTICS
New text highlighted in red:
4.4 Special warnings and precautions for use
Concomitant use of systemic ketoconazole significantly increases systemic exposure to salmeterol. This may lead to an increase in the incidence of systemic effects (e.g. prolongation in 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 of salmeterol treatment (see section 4.5).
Both non-selective and selective beta-blockers should be avoided in patients with asthma unless there are compelling reasons for their use.
Potentially serious hypokalaemia may result from 2 agonist therapy. Particular caution is advised in acute severe asthma as this effect may be potentiated by concomitant treatment with xanthine derivatives, steroids and diuretics.
Potent CYP3A4 inhibitors
Co-administration of ketoconazole (400 mg orally once daily) and salmeterol (50 mcg inhaled twice daily) in 15 healthy subjects for 7 days resulted in a significant increase in plasma salmeterol exposure (1.4-fold Cmax and 15-fold AUC). This may lead to an increase in the incidence of other systemic effects of salmeterol treatment (e.g. prolongation of QTc interval and palpitations) compared with salmeterol or ketoconazole treatment alone (see Section 4.4).
Clinically significant effects were not seen on blood pressure, heart rate, blood glucose and blood potassium levels. Co-administration with ketoconazole did not increase the elimination half-life of salmeterol or increase salmeterol accumulation with repeat dosing.
The concomitant administration of ketoconazole should be avoided, unless the benefits outweigh the potentially increased risk of systemic side effects of salmeterol treatment. There is likely to be a similar risk of interaction with other potent CYP3A4 inhibitors (e.g. itraconazole, telithromycin, ritonavir).
Co-administration of erythromycin (500mg orally three times a day) and salmeterol (50g inhaled twice daily) in 15 healthy subjects for 6 days resulted in a small but non-statistically significant increase in salmeterol exposure (Cmax mean ratio was 1.40). Co-administration with erythromycin was not associated with any serious adverse effects.
Addition of TORCH study results to section 5.1 of Serevent Evohaler SPC
1.NAME OF THE MEDICINAL PRODUCT
mg has been changes to micrograms
4.2 Posology and method of administration
Addition of practical instructions for Evohaler use
5.2 Pharmacokinetic properties
Fluticasone propionate:
The following line changed from:
The absolute bioavailability of inhaled fluticasone propionate in healthy subjects varies between approximately 10-30 % of the nominal dose depending on the inhalation device used.
To : The absolute bioavailability of a single dose of inhaled fluticasone propionate in healthy subjects varies between approximately 5-11% of the nominal dose depending on the inhalation device used.
6.4 Special precautions for storage
The following line has been added:
Replace the mouthpiece cover firmly and snap it into position.
Serevent Evohaler is for inhalation use only.
Serevent Evohaler should be used regularly. The full benefits of treatment will be apparent after several doses of the medicinal product. As there may be adverse reactions associated with excessive dosing with this class of medicinal product, the dosage or frequency of administration should only be increased on medical advice.
Recommended Doses:
Asthma
Adults and adolescents 12 years and older:
Two actuations of 25 micrograms salmeterol twice daily.
In asthma patients with more severe airways obstruction up to four inhalations of 25 micrograms of salmeterol twice daily may be of benefit.
Children aged 4 years and older:
Children below 4 years of age:
Serevent Evohaler is not recommended for use in children below four years of age due to insufficient data on safety and efficacy.
COPD
Adults:
Children:
Special patient groups:
There is no need to adjust the dose in elderly patients or in those with renal impairment. There are no data available on the use of Serevent Evohaler in patients with hepatic impairment.
INSTRUCTIONS FOR USE:
Patients should be carefully instructed in the proper use of their inhaler (see Patient Information Leaflet).
Patients should remove the mouthpiece cover by gently squeezing the sides of the cover
Patients should check inside and outside of the inhaler including the mouthpiece for the presence of loose objects.
Patients should shake the inhaler well
Patients should hold the inhaler upright between fingers and thumb with their thumb on the base, below the mouthpiece.
Patients should breathe out as far as is comfortable and then place the mouthpiece in their mouth between their teeth and close their lips around it. Patients should be instructed not to bite the mouthpiece.
Just after starting to breathe in through their mouth patients should press down on the top of the inhaler to release salmeterol while still breathing in steadily and deeply.
While holding their breath, patients should take the inhaler from their mouth and take their finger from the top of the inhaler. They should continue holding their breath for as long as is comfortable.
If patients are going to take a further puff, they should keep the inhaler upright and wait about half a minute before repeating steps
After use patients should always replace the mouthpiece cover to keep out dust and fluff.
Patients should replace Tt
Important:
Patients should not rush stages
Patients should practise in front of a mirror for the first few times. If they see "mist" coming from the top of their inhaler or the sides of their mouth they should start again from stage 2.
Serevent Evohaler should be used with a Volumatic spacer device by patients who find it difficult to synchronise aerosol actuation with inspiration of breath which is often the case for children and the elderly.
Cleaning:
The inhaler should be cleaned at least once a week by:
1.
2.
3.
The canister must not be removed from the plastic casing when cleaning the inhaler.
PATIENTS MUST NOT PUT THE METAL CANISTER INTO WATER.
Do not store above 30 C.
The canister contains a pressurised liquid. Do not expose to temperatures higher than 50oC. Do not pierce the canister.
Pressurised container.
6.6 Special precautions for disposal
No special requirements.