Description
Bexitrol®F fflAXHAlER®
Salmeterol and Fluticasone Propionate
Inhalation Powder, Pre-dispensed
Read all of this leaflet carefully before you start taking this medicine because it contains important information for you. Keep this leaflet. You may need to read it again. If you have any further questions, ask your doctor.
Description
Bexitrol® F Maxhaler® is a combination of Salmeterol Xinafoate BP and Fluticasone Propionate BP. Salmeterol Xinafoate is a selective, long-acting p, agonist used in the treatment of asthma and other forms of diffuse airway obstruction. Fluticasone Propionate is a corticosteroid with mainly glucocorticoid activity. Fluticasone Propionate is stated to exert a topical effect on the lungs without systemic effects at the usual dose. Maxhaler® is a molded plastic device containing a foil strip with 60 regularly placed blisters containing pre-dispensed inhalation powder.
Indications
Asthma
Bexitrol® F is indicated in the regular treatment of asthma where the use of a combination product (long-acting P2 agonist and inhaled corticosteroid) is appropriate:
- Patients not adequately controlled with inhaled corticosteroids and ‘as needed’ inhaled short-acting p2agonist, or
- Patients already adequately controlled on both inhaled corticosteroid and long-acting p2agonist
Bexitrol®F 50/100 119 is not appropriate in adults and children with severe asthma.
Chronic Obstructive Pulmonary Disease (COPD)
Bexitrol®Fis indicated for the symptomatic treatment of patients with COPD, with an FEV1 <60% predicted normal (pre-bronchodilator) and a history of repeated exacerbations, who have significant symptoms despite regular bronchodilator therapy.
Dosage and Administration
Patients should be made aware that Bexitrol®F Maxhaler®must be used daily for optimum benefit, even when asymptomatic.
Asthma
Adults and Adolescents (12 years and older)
Bexitrol®F 50/100 Maxhaler®: One Inhalation twice daily Bexitrol®F 50/250 Maxhaler®: One Inhalation twice daily Bexitrol®F 50/500 Maxhaler®: One Inhalation twice daily Children (4 years and older)
Bexitrol®F 50/100 Maxhaler®: One Inhalation twice daily
The maximum licensed dose of fluticasone propionate delivered by Bexitrol®F Maxhaler®in children is100 119 twice daily.
There are no data available for use of Bexitrol®F in children aged under 4 years.
COPD
Adults
Bexitrol®F 50/500 Maxhaler®: One Inhalation twice daily
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 for use of Bexitrol®F in patients with hepatic impairment.
Using the Maxhaler®: This is a patient-friendly, ready-to-use, and easy-to-grip device. Use as per instructions for use.
Contraindication
Bexitrol®F has contraindicated in patients with a history of hypersensitivity to any of the ingredients.
Special Warnings and Special Precautions
Deterioration of disease
Bexitrol®F Maxhaler®should not be used to treat acute asthma symptoms for which a fast- and short-acting bronchodilator is required. Patients should be advised to have their inhaler to be used for relief in an acute asthma attack available at all times.
Patients should not be initiated onBexitrol®F Maxhaler®during an exacerbation, or if they have significantly worsening or acutely deteriorating asthma.
Serious asthma-related adverse events and exacerbations may occur during treatment with Bexitrol®F. Patients should be asked to continue treatment but to seek medical advice if asthma symptoms remain uncontrolled or worsen after initiation on Bexitrol®F.
For patients with COPD experiencing exacerbations, treatment with systemic corticosteroids is typically indicated, therefore patients should be instructed to seek medical attention if symptoms deteriorate with Bexitrot:!IF>. Treatment with Bexitrol®F should not be stopped abruptly in patients with asthma due to the risk of exacerbation. Therapy should be down-titrated under physician supervision.
As with all inhaled medication containing corticosteroids, Bexitrol® F should be administered with caution in patients with active or quiescent pulmonary
tuberculosis and fungal, viral, or other infections of the airway. Appropriate treatment should be promptly instituted if indicated.
Cardiovascular effects: Rarely, Bexitrol®F may cause cardiac arrhythmias e.g. supraventricular tachycardia, extrasystoles, and atrial fibrillation, and a mild transient reduction in serum potassium at high therapeutic doses. Bexitrol® F should be used with caution in patients with severe cardiovascular disorders or heart rhythm abnormalities and in patients with diabetes mellitus, thyrotoxicosis, uncorrected hypokalaemia, or patients predisposed to low levels of serum potassium.
Hyperglycemia: There have been very rare reports of increases in blood glucose levels and this should be considered when prescribing to patients with a history of diabetes mellitus.
Paradoxical bronchospasm: As with other inhalation therapy paradoxical
bronchospasm may occur with an immediate increase in wheezing and shortness of breath after dosing. Paradoxical bronchospasm responds to a rapid-acting bronchodilator and should be treated straight away. Bexitrol®F Maxhaler®should be discontinued immediately, the patient assessed and alternative therapy instituted if necessary.
The pharmacological side effects of P2 agonist treatment, such as tremors,
palpitations, and headaches, have been reported, but tend to be transient and reduce with regular therapy.
Systemic Corticosteroid Effects: Systemic effects may occur with any inhaled corticosteroid, particularly at high doses prescribed for long periods. These effects are much less likely to occur than with oral corticosteroids. Possible systemic effects include Cushing’s syndrome, Cushingoid features, adrenal suppression, decrease in bone mineral density, cataracts, and glaucoma, and more rarely, a range of psychological or behavioral effects including psychomotor hyperactivity, sleep disorders, anxiety, depression or aggression (particularly in children) It is important, therefore, that the patient is reviewed regularly and the dose of inhaled corticosteroid is reduced to the lowest dose at which effective control of asthma is maintained.
Prolonged treatment of patients with high doses of 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 1000 micrograms. Situations, which could potentially trigger acute adrenal crisis include trauma, surgery, infection or any rapid reduction in dosage. Presenting symptoms are typically vague and may include anorexia, abdominal pain, weight loss, tiredness, headache, nausea, vomiting, hypotension, decreased level of consciousness, hypoglycemia, and seizures. Additional systemic corticosteroid cover should be considered during periods of stress or elective surgery.
The benefits of inhaled fluticasone propionate therapy should minimize the need for oral steroids, but patients transferring from oral steroids may remain at risk of impaired adrenal reserve for a considerable time. Therefore these patients should be treated with special care and adrenocortical function regularly monitored. Patients who have required high-dose emergency corticosteroid therapy in the past may also be at risk. This possibility of residual impairment should always be borne in mind in emergency and elective situations likely to produce stress, and appropriate corticosteroid treatment must be considered. The extent of the adrenal impairment may require specialist advice before elective procedures.
Ritonavir can greatly 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 corticosteroid side effects. There is also an increased risk of systemic side effects when combining fluticasone propionate with other potent CYP3A inhibitors.
Pneumonia in patients with COPD: An increase in the incidence of pneumonia, including pneumonia requiring hospitalization, has been observed in patients with COPD receiving inhaled corticosteroids. There is some evidence of an increased risk of pneumonia with increasing steroid dose but this has not been demonstrated conclusively across all studies. There is no conclusive clinical evidence for intra-class differences in the magnitude of the pneumonia risk among inhaled corticosteroid products. Physicians should remain vigilant for the possible development of pneumonia in patients with COPD as the clinical features of such infections overlap with the symptoms of COPD exacerbations.
Risk factors for pneumonia in patients with COPD include current smoking, older age, low body mass index (BMI), and severe COPD.
Interactions with potent CYP3A4 inhibitors: 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 OTc 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.
Pediatric Population
Children and adolescents <16 years taking high doses of fluticasone propionate
(typically; 1000 micrograms/day) maybe at particular risk. Systemic effects may occur, particularly at high doses prescribed for long periods. Possible systemic effects include Cushing’s syndrome, Cushingoid features, adrenal suppression, acute adrenal crisis, and growth retardation in children and adolescents, and more rarely, a range of psychological or behavioral effects including psychomotor hyperactivity, sleep disorders, anxiety, depression, or aggression. Consideration should be given to referring the child or adolescent to a pediatric respiratory specialist.
It is recommended that the height of children receiving prolonged treatment with inhaled corticosteroids is regularly monitored. The dose of inhaled corticosteroids should be reduced to the lowest dose at which effective control of asthma is maintained.
Drug Interaction
p adrenergic blockers may weaken or antagonize the effect of Salmeterol. Both non-selective and selective P blockers should be avoided unless there are compelling reasons for their use. Potentially serious hypokalaemia may result from P2 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. Concomitant use of other adrenergic-containing drugs can have a potentially additive effect.
Fluticasone propionate and Salmetarol are substrates of CYP3A4. The use of strong CYP3A4 inhibitors (e.g. ritonavir, clarithromycin, nelfinavir, ketoconazole, etc.) with Bexitrol®F Maxhaler®is not recommended because increased systemic corticosteroid and increased cardiovascular adverse effects may occur.
Pregnancy and Lactation
Pregnancy
A large amount of data on pregnant women (more than 1000 pregnancy outcomes) indicates no malformative or neonatal toxicity related to Bexitrol®F. Animal studies have shown reproductive toxicity after the administration of P2 adrenoreceptor agonists and glucocorticosteroids.
Administration of Bexitrol®F to pregnant women should only be considered if the expected benefit to the mother is greater than any 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.
Breastfeeding
It is unknown whether Salmeterol and fluticasone propionate/metabolites are excreted in human milk. Studies have shown that Salmeterol and fluticasone propionate, and their metabolites, are excreted into the milk of lactating rats. A risk to breastfed newborn infants cannot be excluded. A decision must be made whether to discontinue breastfeeding or to discontinue Bexitrol®F therapy taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.
Side Effects
As Bexitrol®F Maxhaler®contains salmeterol and fluticasone propionate, the type and severity of adverse reactions associated with each of the compounds may be expected. There is no incidence of additional adverse events following the concurrent administration of the two compounds.
The following side effects were commonly reported: Candidiasis of the mouth and throat, Pneumonia (in COPD patients), Bronchitis, Hypokalaemia, Headache, Nasopharyngitis, Throat irritation, Hoarseness/dysphonia, Sinusitis, Contusions, Muscle cramps, Traumatic fractures, Arthralgia and Myalgia.
The following side effects were rarely reported: Paradoxical bronchospasm, Oesophageal candidiasis, Angioedema (mainly facial and oropharyngeal edema), Respiratory symptoms (bronchospasm), Anaphylactic reactions including anaphylactic shock, Cushing’s syndrome, Cushingoid features, Adrenal suppression, Growth retardation in children and adolescents, Decreased bone mineral density, Behavioural changes, including psychomotor hyperactivity and irritability (predominantly in children), Glaucoma, Cardiac arrhythmias (including supraventricular tachycardia and extrasystoles).
Overdosage
There are no data available from clinical trials on overdose with Bexitrol®F Maxhaler®.
Pharmaceutical Precautions
Avoid storage in direct sunlight or heat. Do not store above 30’C. Store in a dry place. Keep away from children. Store your Maxhaler®in Carry-bag and always keep your information leaflet inside.
Special precautions for disposal and another handling
Do not open until you are ready to inhale it because after each opening of the mouthpiece cover one dose is opened and your device will be clogged if it is not inhaled. If you accidentally open the mouthpiece cover/ lever make sure to gently shake by holding the mouthpiece downward to remove the extra powder.
The Maxhaler®releases a powder which is inhaled into the lungs. A dose indicator on the Maxhaler®indicates the number of doses left.
Commercial Pack
Bexitrol®F 50/100 Maxhaler®: One Maxhaler® contains 60 doses and each dose
contains Salmeterol Xinafoate BP equivalent to Salmeterol 50 µg and Fluticasone Propionate BP 100 µg.
Bexitrol®F 50/250 Maxhaler®: One Maxhaler®contains 60 doses and each dose contains Salmeterol Xinafoate BP equivalent to Salmeterol 50 rig and Fluticasone Propionate BP 250 µg.
Bexitrol®F 50/500 Maxhaler®: One Maxhaler®contains 60 doses and each dose contains Salmeterol Xinafoate BP equivalent to Salmeterol 50119 and Fluticasone Propionate BP 500 r,g.
- exitrol® F Maxhaler® is for oral inhalation use only.
- Take Bexitrol®F Maxhaler®out of the foil pouch just before you use it for the first time. Safely throw away the pouch. The Maxhaler® will be in the closed position. The counter should read
- You should consider getting a replacement when the counter shows the number
- Do not use your Maxhaler®if the counter shows 00and must dispose of your
Maxhaler®.
- Do not open unless used. Otherwise, there will be a chance of wasting a dose which may retain inside the device and lead to cause an overdose in the next dose.
- However, if there is an accidental opening of the mouthpiece cover, you must hold the device down and then gently shake it to clear the powder from
- You will get a carry bag to store your Maxhaler®device.
