Flovent® HFA

Fluticasone Propionate

Corticosteroid for Oral Inhalation

GlaxoSmithKline

http://www.gsk.com/index.htm

Flovent Monograph PDF download here.

 

Flovent® Diskus®

Fluticasone Propionate

Corticosteroid for Oral Inhalation

GlaxoSmithKline

 

CPS:PIS_m217500

Date of Preparation: July 20, 2001

Date of Revision: December 5, 2003

 

 

Pharmacology

Fluticasone propionate is a highly potent glucocorticoid anti-inflammatory steroid. When administered by inhalation at therapeutic dosages, it has a direct potent anti-inflammatory action within the lungs, resulting in reduced symptoms and exacerbations of asthma and less adverse effects than systemically administered corticosteroids.

     In comparisons with beclomethasone dipropionate, fluticasone propionate has demonstrated greater topical potency.

     Following intravenous administration, the pharmacokinetics of fluticasone propionate are proportional to the dose. Fluticasone propionate is extensively distributed within the body. The volume of distribution at steady state is approximately 300 litres and has a very high clearance which is estimated to be 1.1 litre/minute indicating extensive hepatic extraction. Peak plasma fluticasone propionate concentrations are reduced by approximately 98% within 3-4 hours and only low plasma concentrations are associated with the terminal half-life, which is approximately 8 hours.

     Following oral administration of fluticasone propionate, 87-100% of the dose is excreted in the faeces. Following doses of either 1 or 16 mg, up to 20% and 75% respectively, is excreted in the faeces as the parent compound. There is a non-active major metabolite. Absolute oral bioavailability is negligible (< 1%) due to a combination of incomplete absorption from the gastrointestinal tract and extensive first-pass metabolism.

     Following inhaled dosing in healthy volunteers, absolute systemic bioavailability of fluticasone propionate varies between approximately 10-30% of the nominal dose depending on the inhalation device used. In patients, a lesser degree of systemic exposure to inhaled fluticasone propionate has been observed. Systemic absorption of fluticasone propionate occurs mainly through the lungs, and is initially rapid, then prolonged.

     The plasma protein binding of fluticasone propionate is 91%. Fluticasone propionate is extensively metabolised by CYP3A4 enzyme to an inactive carboxylic acid derivative. As fluticasone propionate is given at very low doses, any effect on co-administered drugs is unlikely (see Precautions, Drug Interactions).

 

Indications

FLOVENT (fluticasone propionate) is indicated for the prophylactic management of steroid-responsive bronchial asthma in adults and children.

Adults and Adolescents 16 Years of Age and Older

Mild Asthma

PEF values greater than 80% of predicted at baseline with less than 20% variability. Patients requiring intermittent symptomatic bronchodilator asthma medication on more than an occasional basis.

Moderate Asthma

PEF values 60-80% of predicted at baseline with 20-30% variability. Patients requiring regular asthma medication and patients with unstable or worsening asthma on currently available prophylactic therapy or bronchodilator alone.

Severe Asthma

PEF values less than 60% of predicted at baseline with greater than 30% variability. Patients with severe, chronic asthma. On introduction of inhaled fluticasone propionate, many patients who are dependent on systemic corticosteroids for adequate control of symptoms may be able to reduce significantly or to eliminate their requirements for oral corticosteroids.

     Severe asthma requires regular medical assessment as death may occur. Patients with severe asthma have constant symptoms and frequent exacerbations, with limited physical capacity. These patients will require high dose inhaled (see Dosage) or oral corticosteroid therapy. Sudden worsening of symptoms may require increased corticosteroid dosage which should be administered under urgent medical supervision.

Children 4 Years of Age and Older

FLOVENT DISKUS is indicated for any child 4 years of age and older who requires prophylactic medication, including patients not controlled on currently available prophylactic medication.

Children 12 Months of Age and Older

FLOVENT HFA inhalation aerosol is indicated for children 12 months of age and above who require prophylactic medication, including patients not controlled on currently available prophylactic medication.

 

Contraindications

FLOVENT (fluticasone propionate) is contraindicated in patients with a history of hypersensitivity to any of its ingredients and in patients with untreated fungal, bacterial or tuberculous infections of the respiratory tract.

     FLOVENT DISKUS inhalation powder contains lactose (which contains milk protein) (see Supplied) and is therefore contraindicated in patients with IgE mediated allergic reactions to lactose or milk.

     Not to be used in the primary treatment of status asthmaticus or other acute episodes of asthma, or in patients with moderate to severe bronchiectasis.

 

Warnings

Systemic Steroid Replacement by Inhaled Steroid

Particular care is needed in asthmatic patients who are transferred from systemically active corticosteroids to inhaled corticosteroids because deaths due to adrenal insufficiency have occurred during and after transfer. For the transfer of patients being treated with oral corticosteroids, FLOVENT (fluticasone propionate) should first be added to the existing oral steroid therapy, which is then gradually withdrawn.

     Patients with adrenocortical suppression should be monitored regularly and the oral steroid reduced cautiously. Some patients transferred from other inhaled steroids or oral steroids remain at risk of impaired adrenal reserve for a considerable time after transferring to inhaled fluticasone propionate.

     After withdrawal from systemic corticosteroids, a number of months are required for recovery of hypothalamic-pituitary-adrenal (HPA) function. During this period of HPA suppression, patients may exhibit signs and symptoms of adrenal insufficiency when exposed to trauma, surgery or infections, particularly gastroenteritis. Although FLOVENT may provide control of asthmatic symptoms during these episodes, it does not provide the systemic steroid which is necessary for coping with these emergencies. The physician may consider supplying oral steroids for use in times of stress (e.g. worsening asthma attacks, chest infections, surgery).

     During periods of stress or a severe asthmatic attack, patients who have been withdrawn from systemic corticosteroids should be instructed to resume systemic steroids immediately and to contact their physician for further instruction. These patients should also be instructed to carry a warning card indicating that they may need supplementary systemic steroids during periods of stress or a severe asthma attack. To assess the risk of adrenal insufficiency in emergency situations, routine tests of adrenal cortical function, including measurement of early morning and evening cortisol levels, should be performed periodically in all patients. An early morning resting cortisol level may be accepted as normal only if it falls at or near the normal mean level.

     Transfer of patients from systemic steroid therapy to FLOVENT may unmask allergic conditions outside the pulmonary tract that were previously suppressed by the systemic steroid therapy, e.g., rhinitis, conjunctivitis, and eczema. These allergies should be symptomatically treated with antihistamine and/or topical preparations, including topical steroids.

Candidiasis

Therapeutic dosages frequently cause the appearance of  C.albicans (thrush) in the mouth and throat. The development of pharyngeal and laryngeal candidiasis is a cause for concern because the extent of its penetration into the respiratory tract is unknown. Patients may find it helpful to rinse and gargle with water after using fluticasone propionate. Symptomatic candidiasis can be treated with topical antifungal therapy while still continuing to use FLOVENT (see Precautions, Drug Interactions).

Effect on Infection

Patients who are on drugs that suppress the immune system are more susceptible to infections than healthy individuals. Chickenpox and measles, for example, can have a more serious or even fatal course in susceptible children or adults on corticosteroids. In such children or adults who have not had these diseases, particular care should be taken to avoid exposure. How the dose, route, and duration of corticosteroid administration affect the risk of developing a disseminated infection is not known. The contribution of the underlying disease and/or prior corticosteroid treatment to the risk is also not known. If exposed to chickenpox, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated. If exposed to measles, prophylaxis with intramuscular pooled immunoglobulin (IG) may be indicated. If chickenpox develops, treatment with antiviral agents may be considered.

Paradoxical Bronchospasm

As with other inhalation therapy, paradoxical bronchospasm may occur characterized by an immediate increase in wheezing after dosing. This should be treated immediately with a fast-acting inhaled bronchodilator (e.g. salbutamol) to relieve acute asthmatic symptoms. FLOVENT should be discontinued immediately, the patient assessed, and if necessary, alternative therapy instituted.

Monitoring Asthma Control

Increasing use of short-acting inhaled bronchodilators to control symptoms indicates deterioration of asthma control. Sudden and progressive deterioration in asthma control is potentially life-threatening and consideration should be given to increasing corticosteroid dosage. Patients should be instructed to contact their physicians if they find that relief with short-acting bronchodilator treatment becomes less effective or they need more inhalations than usual. During such episodes, patients may require therapy with systemic corticosteroids.

     FLOVENT is not indicated for rapid relief of bronchospasm but for regular daily treatment of the underlying inflammation. Patients will require a fast and short acting inhaled bronchodilator (e.g. salbutamol) to relieve acute asthmatic symptoms. There is no evidence that control of bronchial asthma can be achieved by the administration of FLOVENT in amounts greater than the recommended dosages.

     Lack of response or severe exacerbations of asthma should be treated by increasing the dose of FLOVENT and, if necessary, by giving a systemic steroid and/or an antibiotic if there is an infection.

Drug Interactions

A drug interaction study of intranasal fluticasone propionate in healthy subjects has shown that ritonavir (a highly potent cytochrome P450 3A4 inhibitor) can greatly increase fluticasone propionate plasma concentrations, resulting in markedly reduced serum cortisol concentrations. During post-marketing use, there have been reports of clinically significant drug interactions in patients receiving intranasal and inhaled fluticasone propionate and ritonavir, resulting in systemic corticosteroid effects including Cushing’s syndrome and adrenal suppression. Therefore, concomitant use of fluticasone propionate and ritonavir should be avoided, unless the potential benefit to the patient outweighs the risk of systemic corticosteroid side-effects.

 

Precautions

 

General

It is essential that the patients be instructed that FLOVENT (fluticasone propionate) is a preventative agent which must be taken daily at the intervals recommended by their doctors and is not to be used as acute treatment for an asthmatic attack.

     Patients should be advised to inform subsequent physicians of the prior use of corticosteroids.

     As with all non-CFC metered-dose inhalers, it is important that asthma control and adverse reactions be re-assessed by the physician when switching from an inhaler formulated with CFC propellant to one with non-CFC propellant.

Systemic Steroid Replacement by Inhaled Steroid

The replacement of a systemic steroid with inhaled steroid must be gradual and carefully supervised by the physician since upon withdrawal systemic symptoms (e.g. joint and/or muscular pain, lassitude, depression) may occur despite maintenance or improvement of respiratory function. The guidelines under Dosage should be followed in all such cases.

Systemic 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 (see Overdose: Symptoms and Treatment). Possible systemic effects include adrenal suppression, growth retardation in children and adolescents, decrease in bone mineral density, cataract and glaucoma. It is important, therefore, that the dose of inhaled corticosteroid is titrated to the lowest dose at which effective control is maintained (see Adverse Effects).

     The possibility of impaired adrenal response should always be borne in mind in emergency and elective situations likely to produce stress and appropriate corticosteroid treatment must be considered (see Overdose: Symptoms and Treatment).

     Certain individuals can show greater susceptibility to the effects of inhaled corticosteroid than do most patients.

Long-Term Effects

The long-term effects of fluticasone propionate in human subjects are still unknown. In particular, the local effects of the drug on developmental or immunologic processes in the mouth, pharynx, trachea, and lungs are unknown. There is also no information about the possible long-term systemic effects of the agent. During long-term therapy, HPA axis function and haematological status should be assessed periodically.

Discontinuance

Treatment with FLOVENT should not be stopped abruptly, but tapered off gradually.

Eosinophilic Conditions

In rare cases, patients on inhaled fluticasone propionate may present with systemic eosinophilic conditions, with some patients presenting with clinical features of vasculitis consistent with Churg-Strauss syndrome, a condition that is often treated with systemic corticosteroid therapy. These events usually, but not always, have been associated with the reduction and/or withdrawal of oral corticosteroid therapy following the introduction of fluticasone propionate. Cases of serious eosinophilic conditions have also been reported with other inhaled corticosteroids in this clinical setting. Physicians should be alert to eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients. A causal relationship between fluticasone propionate and these underlying conditions has not been established.

 

Pregnancy

The safety of fluticasone propionate in pregnancy has not been established. If used, the expected benefits should be weighed against the potential risk to the fetus, particularly during the first trimester of pregnancy.

     Like other glucocorticoids, fluticasone propionate is teratogenic to rodent species. Adverse effects typical of potent corticosteroids are only seen at high systemic exposure levels; administration by inhalation ensures minimal systemic exposure. The relevance of these findings to humans has not yet been established since well-controlled trials relating to foetal risk in humans are not available. Infants born of mothers who have received substantial doses of glucocorticoids during pregnancy should be carefully observed for hypoadrenalism.

 

Lactation

Glucocorticoids are excreted in human milk. The excretion of fluticasone propionate into human breast milk has not been investigated. When measurable plasma levels were obtained in lactating laboratory rats following subcutaneous administration there was evidence of fluticasone propionate in the breast milk. However, plasma levels in patients following inhaled fluticasone propionate at recommended doses are likely to be low. The use of fluticasone propionate in nursing mothers requires that the possible benefits of the drug be weighted against the potential risk to the infant.

 

Children

Fluticasone propionate is not presently recommended for children younger than 12 months of age due to limited clinical data in this age group.

     It is recommended that the height of children receiving prolonged treatment with inhaled corticosteroids is regularly monitored (see Adverse Effects).

Effect on Infection

Corticosteroids may mask some signs of infections and new infections may appear. A decreased resistance to localised infection has been observed during corticosteroid therapy. This may require treatment with appropriate therapy or stopping the administration of fluticasone propionate until the infection is eradicated (see Warnings, Effect on Infection).

Hypothyroidism and Cirrhosis

There is an enhanced effect of corticosteroids on patients with hypothyroidism and in those with cirrhosis.

Use of Corticosteroids and Acetylsalicylic Acid

Acetylsalicylic acid should be used cautiously in conjunction with corticosteroids in hypoprothrombinemia.

Oral Hygiene

In some patients, corticosteroids may cause hoarseness or candidiasis of the mouth and throat (thrush). Adequate oral hygiene is of primary importance in minimizing overgrowth of micro-organisms such as  C. albicans. Patients may find it helpful to rinse and gargle with water after using the inhaler (see Dosage). Symptomatic candidiasis can be treated with topical antifungal therapy while still continuing treatment with FLOVENT (see Drug Interactions).

 

Drug Interactions

Under normal circumstances, low plasma concentrations of fluticasone propionate are achieved after inhaled dosing, due to extensive first pass metabolism and high systemic clearance mediated by cytochrome P450 3A4 in the gut and liver. Hence, clinically significant drug interactions involving fluticasone propionate are unlikely.

     A drug interaction study of intranasal fluticasone propionate in healthy subjects has shown that ritonavir (a highly potent cytochrome P450 3A4 inhibitor) can greatly increase fluticasone propionate plasma concentrations, resulting in markedly reduced serum cortisol concentrations. During post-marketing use, there have been reports of clinically significant drug interactions in patients receiving intranasal and inhaled fluticasone propionate and ritonavir, resulting in systemic corticosteroid effects including Cushing’s syndrome and adrenal suppression. Therefore, concomitant use of fluticasone propionate and ritonavir should be avoided, unless the potential benefit to the patient outweighs the risk of systemic corticosteroid side-effects.

     Studies have shown that other inhibitors of cytochrome P450 3A4 produce negligible (erythromycin) and minor (ketoconazole) increases in systemic exposure to fluticasone propionate without notable reductions in serum cortisol concentrations. Nevertheless, care is advised when co-administering potent cytochrome P450 3A4 inhibitors (e.g. ketoconazole) as there is potential for increased systemic exposure to fluticasone propionate.

Information to be Provided to the Patient

To ensure the proper dosage and administration of the drug, the patient must be instructed by a physician or other health professional in the use of the inhalation aerosol and DISKUS (see Information for the Patient).

     Inhaler actuation should be synchronised with inspiration to ensure optimum delivery of the drug to the lungs. Additionally, patients could use a spacer device such as VENT-A-HALER.

Patients should be given the following information on FLOVENT HFA inhalation aerosol:

1. It may take several days for this medicine to work and is very important that it is used regularly as instructed. Do not stop treatment unless told to do so by a doctor.

2. Do not use this medicine to treat a sudden attack of breathlessness.

3. It is important that patients be reassured that FLOVENT HFA inhalation aerosol is a safe and effective product, even though they may notice a slightly different taste or spray force compared to FLOVENT inhalation aerosol (CFC formulation).

4. Common adverse events include hoarseness, candidiasis and sore throat. Patients should be instructed to rinse and gargle with water immediately after taking each dose.

5. Use FLOVENT HFA inhalation aerosol only with the actuator supplied with the product. Discard canister after 60 sprays have been used for the 60 dose canister or 120 sprays for the 120 dose canister.

 

 

Adverse Effects

In general, inhaled corticosteroid therapy may be associated with dose dependent increases in the incidence of ocular complications, reduced bone density, suppression of HPA axis responsiveness to stress, and inhibition of growth velocity in children. Such events have been reported rarely in clinical trials with fluticasone propionate.

     Glaucoma may be exacerbated by inhaled corticosteroid treatment for asthma or rhinitis. In patients with established glaucoma who require long-term inhaled corticosteroid treatment, it is prudent to measure intraocular pressure before commencing the inhaled corticosteroid and to monitor it subsequently. In patients without established glaucoma, but with a potential for developing intraocular hypertension (e.g. the elderly), intraocular pressure should be monitored at appropriate intervals.

     In elderly patients treated with inhaled corticosteroids, the prevalence of posterior subcapsular and nuclear cataracts is probably low but increases in relation to the daily and cumulative lifetime dose. Cofactors such as smoking, ultraviolet B exposure, or diabetes may increase the risk. Children may be less susceptible.

     A reduction of growth velocity in children or teenagers may occur as a result of inadequate control of chronic diseases such as asthma or from use of corticosteroids for treatment. Physicians should closely follow the growth of all children taking corticosteroids by any route and weigh the benefits of corticosteroid therapy and asthma control against the possibility of growth suppression if any child’s or adolescent’s growth appears slowed.

     Osteoporosis and fracture are the major complications of long-term asthma treatment with parenteral or oral steroids. Inhaled corticosteroid therapy is also associated with dose-dependent bone loss although the degree of risk is very much less than with oral steroid. This risk may be offset by estrogen replacement in post-menopausal women, and by titrating the daily dose of inhaled steroid to the minimum required to maintain optimal asthma control. It is not yet known whether the peak bone density achieved during youth is adversely affected if substantial amount of inhaled corticosteroid are administered prior to 30 years of age. Failure to achieve maximal bone density during youth could increase the risk of osteoporotic fracture when those individuals reach 60 years of age and older.

     No major side effects attributable to the use of FLOVENT (fluticasone propionate) have been reported. Adverse reactions in controlled clinical studies with FLOVENT have been primarily those normally associated with asthma. Apart from asthma and related events and pharmacologically predicted events (candidiasis and hoarseness), there were no dose-related trends. There have been uncommon reports of cutaneous hypersensitivity reactions. There have also been rare reports of hypersensitivity reactions manifesting as angioedema (mainly facial and oropharyngeal edema), respiratory symptoms (dyspnea and/or bronchospasm) and very rarely, anaphylactic reactions. The adverse reactions reported by patients treated with FLOVENT were similar to those reported by patients treated with beclomethasone dipropionate.

      Table 1 lists adverse events considered by the investigator to be potentially drug-related that occurred at a rate of 3% or greater in any treatment group during clinical trials comparing FLOVENT HFA inhalation aerosol and FLOVENT (fluticasone propionate) inhalation aerosol (CFC formulation) at a dosage of 500 µg twice daily for one year. FLOVENT DISKUS adverse event profile is similar in incidence and nature at 500 µg bid for 4 weeks.

CPS:FloventHFADiskus_t1Click here for Table 1

Table 1: FLOVENT

Adverse Experience Incidence (% of patients) in Clinical Trials in Adolescent and Adult Patients

 

Adverse Event	FLOVENT HFA 500 µg bid (n=366)	FLOVENTa 500 µg bid (n=371)	FLOVENT DISKUS 500 µg bid (n=443)
Hoarseness/Dysphonia	7%	7%	1.5%
Oral candidiasis	6%	7%	< 1%
Asthma & related events	6%	5%	1%
Sore Throat	4%	2%	< 1%

 

 ^a FLOVENT (fluticasone propionate) inhalation aerosol formulated with CFC propellants.

 

 

     In children 4-17 years of age, receiving FLOVENT DISKUS, the incidence of drug-related adverse events were similar in incidence and nature to that seen in adults.

     In children, 4 to 16 years of age, receiving FLOVENT HFA inhalation aerosol versus FLOVENT inhalation aerosol (CFC formulation), the incidence and nature of adverse events were similar in each treatment group. The most commonly reported events were upper respiratory tract infection, headache, viral infections, throat irritation and rhinitis.

     In children, 12 months to 4 years of age, receiving FLOVENT HFA inhalation aerosol the nature of adverse events were as expected for this subject population. The majority of the adverse events reported were primarily from the ear, nose and throat and lower respiratory body systems. The most commonly reported adverse events were upper respiratory tract infection, cough, fever, asthma and rhinitis.

     Overall, the incidence and nature of the adverse events reported for FLOVENT HFA and FLOVENT inhalation aerosol CFC formulation were similar.

Eosinophilic Conditions

In rare cases, patients on inhaled fluticasone propionate may present with systemic eosinophilic conditions, with some patients presenting with clinical features of vasculitis consistent with Churg-Strauss syndrome, a condition that is often treated with systemic corticosteroid therapy. These events usually, but not always, have been associated with the reduction and/or withdrawal of oral corticosteroid therapy following the introduction of fluticasone propionate. Cases of serious eosinophilic conditions have also been reported with other inhaled corticosteroids in this clinical setting. Physicians should be alert to eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients. A causal relationship between fluticasone propionate and these underlying conditions has not been established.

 

Overdose

 

 

Symptoms

Acute inhalation of fluticasone propionate doses in excess of those approved may lead to temporary suppression of the hypothalamic-pituitary-adrenal axis. This does not usually require emergency action, as normal adrenal function typically recovers within a few days.

     If higher than approved doses are continued over prolonged periods, significant adrenocortical suppression is possible. There have been very rare reports of acute adrenal crisis occurring in children exposed to higher than approved dosages (typically 1000 µg daily and above), over prolonged periods (several months or years); observed features included hypoglycemia and sequelae of decreased consciousness and/or convulsions. Situations which could potentially trigger acute adrenal crisis include exposure to trauma, surgery or infection or any rapid reduction in dosage. Patients receiving higher than approved dosages should be managed closely and the dose reduced gradually.

     Chronic use of inhaled fluticasone propionate in daily doses in excess of the recommended dosage may lead to some degree of adrenal suppression. Monitoring of adrenal reserve may be indicated. Gradual reduction of the inhaled dose may be required. Treatment with inhaled FLOVENT should be continued at a dose sufficient to control asthma.

 

 

Treatment

See Symptoms.

 

Dosage

General

The lowest dose of fluticasone propionate required to maintain good asthma control should be used. When the patient’s asthma is well controlled, a reduction in the dose of fluticasone propionate should be attempted in order to identify the lowest possible dose required to maintain control. Such an attempt at dose reduction should be carried out on a regular basis.

     FLOVENT HFA (fluticasone propionate) Inhalation Aerosol and DISKUS are to be administered by oral inhalation only.

     Since the effect of FLOVENT depends on its regular use and on the proper technique of inhalation, the patient should be made aware of the prophylactic nature of therapy with inhaled fluticasone propionate, and that for optimum benefit FLOVENT should be taken regularly, even when the patient is asymptomatic.

     If patients find that relief with short-acting bronchodilator treatment becomes less effective or they need more inhalations than usual, medical attention should be sought.

     Patients using inhaled bronchodilators should be advised to use the bronchodilator before the FLOVENT in order to enhance the penetration of FLOVENT into the bronchial tree. Several minutes should lapse between the use of the two inhalers to allow for some bronchodilation to occur.

     In the presence of excessive mucous secretion, the drug may fail to reach the bronchioles. Therefore, if an obvious response is not obtained after ten days, a short course of systemic corticosteroid treatment might be in order. Continuation of treatment with inhaled fluticasone propionate usually maintains the improvement achieved, the systemic steroid being gradually withdrawn.

     As a general rule, rinsing the mouth and gargling with water after each inhalation with water can help in preventing the occurrence of candidiasis. Cleansing dentures has the same effect.

     Treatment with FLOVENT should not be stopped abruptly, but tapered off gradually.

Administration

Patients must be instructed, as described in the section Information for the Patient, in the correct method of using FLOVENT HFA Inhalation Aerosol or DISKUS to ensure that the drug reaches the target areas within the lungs.

Inhalation Aerosol

When using FLOVENT HFA inhalation aerosol, each prescribed dose is usually given by a minimum of 2 inhalations. Before the first use, and after periods of greater than seven days without use, the inhaler should be primed before treatment by actuating the inhaler once.

     Inhalation aerosol actuation should be synchronised with inspiration to ensure optimum delivery of drug to the lungs. In patients who find co-ordination of a pressurized metered dose inhaler difficult, a spacer device such as VENT-A-HALER may be used with FLOVENT HFA inhalation aerosol. The use of the open-mouth technique to administer FLOVENT HFA inhalation aerosol has not been investigated in clinical trials.

DISKUS

FLOVENT DISKUS is a device for delivering the dry powder formulation of fluticasone propionate. When using FLOVENT DISKUS, the usual prescribed dose is one blister (inhalation) twice a day.

Dosage

The dosage of fluticasone propionate should be adjusted according to individual response. For patients whose asthma has been stabilized without the use of a spacer device, continuation of therapy with a spacer may require a dosage adjustment.

Adults and Adolescents 16 Years of Age and Older

Usual dosage is 100 to 500 µg twice daily.

     Patients should be given a starting dose of inhaled fluticasone propionate which is appropriate for the severity of their disease (see Indications) as follows:

Mild asthma: 100 to 250 µg twice daily.

Moderate asthma: 250 to 500 µg twice daily.

Severe asthma: 500 µg twice daily. Very severe patients requiring higher doses of corticosteroids such as those patients currently requiring oral steroids may use doses up to 1000 µg twice daily.

     The dose may then be adjusted until control is achieved or reduced to the minimum effective dose according to the individual response.

     Alternatively, the starting dose of fluticasone propionate may be gauged at half the total daily dose of beclomethasone dipropionate or equivalent as administered by metered-dose inhaler.

     Physicians should be aware that, due to the improved potency of fluticasone propionate, the dose may be different than that required with some other inhaled steroids.

     Onset of effect occurs within 4-7 days, although some benefit may be apparent as soon as 24 hours of the start of treatment with fluticasone propionate for patients who have not previously received inhaled steroids. If no improvement is noted in this time frame, an increase in dose should be considered.

Children 4-16 Years of Age

The usual starting dose is 50 or 100 µg twice daily and many children’s asthma will be well controlled with this regimen. For those patients whose asthma is not sufficiently controlled, additional benefit may be obtained by increasing the DISKUS dose up to 200 µg twice daily. Children should be given a starting dose of inhaled fluticasone propionate which is appropriate for the severity of their disease.

     The dose should be adjusted until control is achieved or reduced to the minimum effective dose according to the individual response. This is particularly important in the younger children with severe symptoms who are receiving the larger daily dose.

     The lowest dose of FLOVENT HFA inhalation aerosol available is 50 µg; therefore, it does not offer the required lowest pediatric dose, in which case an alternative inhalation device of fluticasone propionate should also be considered (e.g. dry powder inhaler).

Children 12 Months to 4 Years of Age

Younger children should be given 100 µg twice daily administered via a pediatric spacer device with a face mask such as a BABYHALER.

     Clinical trials in 12 month to 4 year old children have shown that the optimal control of asthma symptoms is achieved with 100 µg twice daily. Higher doses of inhaled drug are required in younger children compared to older children because of reduced efficiency of drug delivery due to smaller airways, use of a spacer device and increased nasal breathing.

     The diagnosis and treatment of asthma should be kept under regular review.

Special Patient Groups

There is no need to adjust the dose in elderly patients or those with hepatic or renal impairment.

Patients Receiving Systemic Steroids

The transfer of steroid-dependent patients to FLOVENT and their subsequent management needs special care mainly because recovery from impaired adrenocortical function, caused by prolonged systemic therapy, is slow. Patients' bronchial asthma should be stable before being given FLOVENT in addition to the usual maintenance dose of systemic steroid. After about a week, gradual withdrawal of the systemic steroid is started by reducing the daily dose by 1 mg of prednisone, or its equivalent of other corticosteroid, at not less than weekly intervals, if the patient is under close observation. In children, the usual rate of withdrawal is 1 mg of the daily dose of prednisone every eight days when under close supervision. If continuous supervision is not feasible, the withdrawal of the systemic steroid should be slower, approximately 1 mg of the daily dose of prednisone (or equivalent) every ten and every twenty days in adults and in children, respectively. A slow rate of withdrawal cannot be over-emphasized.

     If withdrawal symptoms appear, the previous dose of the systemic drug should be resumed for a week before any further decrease is attempted. Patients who have been treated with systemic steroids for long periods of time or at a high dose may have adrenocortical suppression. In these patients adrenocortical function should be monitored regularly and their dose of systemic steroid reduced cautiously.

     Some patients feel unwell during the withdrawal phase experiencing symptoms such as joint and/or muscular pain, lassitude, and depression, despite maintenance or even improvement of respiratory function. Such patients should be encouraged to persevere with FLOVENT but should be watched carefully for objective signs of adrenal insufficiency such as hypotension and weight loss. If evidence of adrenal insufficiency occurs, the systemic steroid dosage should be boosted temporarily and thereafter further withdrawal should be continued more slowly.

     Transferred patients whose adrenocortical function is impaired should carry a warning card indicating that they need supplementary treatment with systemic steroids during periods of stress, e.g. surgery, chest infection, or severe asthma attack. Consideration should be given to supplying such patients with oral steroids to use in an emergency. The dose of inhaled fluticasone propionate should be increased at this time and then reduced to the maintenance level after the systemic steroid has been discontinued.

     Exacerbations of bronchial asthma which occur during the course of treatment with FLOVENT should be treated with a short course of systemic steroid which is gradually tapered as these symptoms subside. Under stressful conditions or when the patient has a severe exacerbation of bronchial asthma, after complete withdrawal of the systemic steroid, use of the latter must be resumed in order to avoid relative adrenocortical insufficiency.

     There are some patients who cannot completely discontinue the oral corticosteroid. In these cases, a minimum maintenance dosage should be given in addition to FLOVENT.

 

Supplied

Inhalation Aerosol

Each actuation of the pressurized metered-dose inhaler delivers: 50, 125, or 250 µg of fluticasone propionate suspended in propellant HFA-134a (1,1,1,2-tetrafluoroethane). It contains no excipients. This product does not contain chlorofluorocarbons (CFCs) as the propellant. The 50 µg strength of FLOVENT HFA inhalation aerosol is available in 120 dose containers. The 125 µg and 250 µg strengths of FLOVENT HFA inhalation aerosol are available in 60 and 120 dose containers. FLOVENT HFA inhalation aerosol is a pressurized metered-dose inhaler (MDI) consisting of an aluminum canister fitted with a metering valve. Each canister is fitted into the supplied orange actuator/adaptor. A strapcap is fitted over the actuator’s mouthpiece when not in use. Store at room temperature (15 to 30°C). Protect from frost and direct sunlight. Contents under pressure. Container may explode if heated. Do not place in hot water or near radiators, stoves, or other sources of heat. Even when apparently empty, do not puncture or incinerate container or store at temperatures over 30°C. As with most inhaled medications in pressurized canisters, the therapeutic effect of this medication may decrease when the canister is cold.

DISKUS

Each inhalation of the dry powder inhalation device delivers: 50, 100, 250, or 500 µg of fluticasone propionate. It also contains lactose (milk sugar), including milk protein, which acts as the “carrier”. FLOVENT DISKUS is a plastic inhaler device containing a foil strip with 60 blisters. Each blister contains 50, 100, 250, or 500 µg of the active ingredient fluticasone propionate. Store between 2 and 30°C in a dry place. Protect from frost and direct sunlight.