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Flovent HFA (Fluticasone Propionate Inhalation) - Warnings and Precautions

 
 



WARNINGS

1. Transferring patients from systemic corticosteroid therapy. Particular care is needed for patients who have been transferred from systemically active corticosteroids to inhaled corticosteroids because deaths due to adrenal insufficiency have occurred in patients with asthma during and after transfer from systemic corticosteroids to less systemically available inhaled corticosteroids. After withdrawal from systemic corticosteroids, a number of months are required for recovery of HPA function.

Patients requiring oral corticosteroids should be weaned slowly from systemic corticosteroid use after transferring to FLOVENT HFA. In a clinical trial of 168 patients, prednisone reduction was successfully accomplished by reducing the daily prednisone dose on a weekly basis following initiation of treatment with FLOVENT HFA. Successive reduction of prednisone dose was allowed only when lung function; symptoms; and as-needed, short-acting beta-agonist use were better than or comparable to that seen before initiation of prednisone dose reduction. Lung function (FEV1 or AM PEF), beta-agonist use, and asthma symptoms should be carefully monitored during withdrawal of oral corticosteroids. In addition to monitoring asthma signs and symptoms, patients should be observed for signs and symptoms of adrenal insufficiency such as fatigue, lassitude, weakness, nausea and vomiting, and hypotension.

Patients who have been previously maintained on 20 mg or more per day of prednisone (or its equivalent) may be most susceptible, particularly when their systemic corticosteroids have been almost completely withdrawn. During this period of HPA suppression, patients may exhibit signs and symptoms of adrenal insufficiency when exposed to trauma, surgery, or infection (particularly gastroenteritis) or other conditions associated with severe electrolyte loss. Although inhaled corticosteroids may provide control of asthma symptoms during these episodes, in recommended doses they supply less than normal physiological amounts of glucocorticoid (cortisol) systemically and do NOT provide the mineralocorticoid activity that is necessary for coping with these emergencies.

During periods of stress or a severe asthma attack, patients who have been withdrawn from systemic corticosteroids should be instructed to resume oralcorticosteroids (in large doses) immediately and to contact their physicians for further instruction. These patients should also be instructed to carry a warning card indicating that they may need supplementary systemic corticosteroids during periods of stress or a severe asthma attack.

Transfer of patients from systemic corticosteroid therapy to FLOVENT HFA may unmask conditions previously suppressed by the systemic corticosteroid therapy, e.g., rhinitis, conjunctivitis, eczema, arthritis, and eosinophilic conditions. Some patients may experience symptoms of systemically active corticosteroid withdrawal, e.g., joint and/or muscular pain, lassitude, and depression, despite maintenance or even improvement of respiratory function.

2. Bronchospasm. As with other inhaled medications, bronchospasm may occur with an immediate increase in wheezing after dosing. If bronchospasm occurs following dosing with FLOVENT HFA, it should be treated immediately with a fast-acting inhaled bronchodilator. Treatment with FLOVENT HFA should be discontinued and alternative therapy instituted.

Patients should be instructed to contact their physicians immediately when episodes of asthma that are not responsive to bronchodilators occur during the course of treatment with FLOVENT HFA. During such episodes, patients may require therapy with oral corticosteroids.

3. Immunosuppression. Persons who are using 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 coursein susceptible children or adults using corticosteroids. In such children or adults who have not had these diseases or been properly immunized, 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 pooled intramuscular immunoglobulin (IG) may be indicated. (See the respective package inserts for complete VZIG and IG prescribing information.) If chickenpox develops, treatment with antiviral agents may be considered.

4. Drug interaction with ritonavir. A drug interaction study in healthy subjects has shown that ritonavir (a highly potent cytochrome P450 3A4 inhibitor) can significantly increase systemic fluticasone propionate exposure (AUC), resulting in significantly reduced serum cortisol concentrations (see CLINICAL PHARMACOLOGY: Pharmacokinetics: Drug Interactions and PRECAUTIONS: Drug Interactions: Inhibitors of Cytochrome P450). During postmarketing use, there have been reports of clinically significant drug interactions in patients receiving fluticasone propionate and ritonavir, resulting in systemic corticosteroid effects including Cushing syndrome and adrenal suppression. Therefore, coadministration of fluticasone propionate and ritonavir is not recommended unless the potential benefit to the patient outweighs the risk of systemic corticosteroid side effects.

5. FLOVENT HFA should not be used to treatacute symptoms. FLOVENT HFA is not to be regarded as a bronchodilator and is not indicated for rapid relief of bronchospasm.

PRECAUTIONS

General

Orally inhaled corticosteroids may cause a reduction in growth velocity when administered to pediatric patients (see PRECAUTIONS: Pediatric Use).

Fluticasone propionate will often help control asthma symptoms with less suppression of HPA function than therapeutically equivalent oral doses of prednisone. Since fluticasone propionate is absorbed into the circulation and can be systemically active at higher doses, the beneficial effects of FLOVENT HFA in minimizing HPA dysfunction may be expected only when recommended dosages are not exceeded and individual patients are titrated to the lowest effective dose. A relationship between plasma levels of fluticasone propionate and inhibitory effects on stimulated cortisol production has been shown after 4 weeks of treatment with fluticasone propionate inhalation aerosol. Since individual sensitivity to effects on cortisol production exists, physicians should consider this information when prescribing FLOVENT HFA.

Because of the possibility of systemic absorption of inhaled corticosteroids, patients treated with FLOVENT HFA should be observed carefully for any evidence of systemic corticosteroid effects. Particular care should be taken in observing patients postoperatively or during periods of stress for evidence of inadequate adrenal response.

It is possible that systemic corticosteroid effects such as hypercorticism and adrenal suppression (including adrenal crisis) may appear in a small number of patients, particularly when FLOVENT HFA is administered at higher than recommended doses over prolonged periods of time. If such effects occur, the dosage of FLOVENT HFA should be reduced slowly, consistent with accepted procedures for reducing systemic corticosteroids and for management of asthma.

The long-term effects of FLOVENT HFA in human subjects are not fully known. In particular, the effects resulting from chronic use of fluticasone propionate on developmental or immunologic processes in the mouth, pharynx, trachea, and lung are unknown. Some patients have received inhaled fluticasone propionate on a continuous basis in a clinical study for up to 4 years. In clinical studies with patients treated for 2 years with inhaled fluticasone propionate, no apparent differences in the type or severity of adverse reactions were observed after long- versus short-term treatment.

Glaucoma, increased intraocular pressure, and cataracts have been reported in patients following the long-term administration of inhaled corticosteroids, including fluticasone propionate.

In clinical studies with inhaled fluticasone propionate, the development of localized infections of the pharynx with Candida albicans has occurred. When such an infection develops, it should be treated with appropriate local or systemic (i.e., oral antifungal) therapy while remaining on treatment with FLOVENT HFA, but at times therapy with FLOVENT HFA may need to be interrupted.

Inhaled corticosteroids should be used with caution, if at all, in patients with active or quiescent tuberculosis infection of the respiratory tract; untreated systemic fungal, bacterial, viral or parasitic infections; or ocular herpes simplex.

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 (see ADVERSE REACTIONS: Observed During Clinical Practice: Eosinophilic Conditions).

Information for Patients

Patients being treated with FLOVENT HFA should receive the following information and instructions. This information is intended to aid them in the safe and effective use of this medication. It is not a disclosure of all possible adverse or intended effects. It is important that patients understand how to use FLOVENT HFA in relation to other asthma medications they are taking.

  1. Patients should use FLOVENT HFA at regular intervals as directed. Individual patients will experience a variable time to onset and degree of symptom relief and the full benefit may not be achieved until treatment has been administered for 1 to 2 weeks or longer. The patient should not increase the prescribed dosage but should contact the physician if symptoms do not improve or if the condition worsens.
  2. Patients who are pregnant or nursing should contact their physicians about the use of FLOVENT HFA.
  3. Patients should be warned to avoid exposure to chickenpox or measles and if they are exposed to consult their physicians without delay.
  4. In general, the technique for administering FLOVENT HFA to children is similar to that for adults. Children should use FLOVENT HFA under adult supervision, as instructed by the patient’s physician. (See the Information for the Patient leaflet accompanying the product.)
  5. Prime the inhaler before using for the first time by releasing 4 test sprays into the air away from the face, shaking well for 5 seconds before each spray. In cases where the inhaler has not been used for more than 7 days or when it has been dropped, prime the inhaler again by shaking well for 5 seconds and releasing 1 test spray into the air away from the face.
  6. After inhalation, rinse the mouth with water and spit out. Do not swallow.
  7. Clean the inhaler at least once a week after the evening dose. Keeping the canister and plastic actuator clean is important to prevent medicine buildup. (See the cleaning instructions in the Information for the Patient leaflet accompanying the product.)
  8. Use FLOVENT HFA only with the actuator supplied with the product. When the counter reads 020, contact the pharmacist for a refill of medication or consult the physician to determine whether a prescription refill is needed. Discard the inhaler when the counter reads 000. Never try to alter the numbers or remove the counter from the metal canister.
  9. For important summary information and instructions for the proper use of FLOVENT HFA, the patient should carefully read and follow the Information for the Patient leaflet accompanying the product.

Drug Interactions

Inhibitors of Cytochrome P450

Fluticasone propionate is a substrate of cytochrome P450 3A4. A drug interaction study with fluticasone propionate aqueous nasal spray in healthy subjects has shown that ritonavir (a highly potent cytochrome P450 3A4 inhibitor) can significantly increase plasma fluticasone propionate exposure, resulting in significantly reduced serum cortisol concentrations (see CLINICAL PHARMACOLOGY: Pharmacokinetics: Drug Interactions ). During postmarketing use, there have been reports of clinically significant drug interactions in patients receiving fluticasone propionate and ritonavir, resulting in systemic corticosteroid effects including Cushing syndrome and adrenal suppression. Therefore, coadministration of fluticasone propionate and ritonavir is not recommended unless the potential benefit to the patient outweighs the risk of systemic corticosteroid side effects.

In a placebo-controlled crossover study in 8 healthy adult volunteers, coadministration of a single dose of orally inhaled fluticasone propionate (1,000 mcg) with multiple doses of ketoconazole (200 mg) to steady state resulted in increased systemic fluticasone propionate exposure, a reduction in plasma cortisol AUC, and no effect on urinary excretion of cortisol. Caution should be exercised when FLOVENT HFA is coadministered with ketoconazole and other known potent cytochrome P450 3A4 inhibitors.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Fluticasone propionate demonstrated no tumorigenic potential in mice at oral doses up to 1,000 mcg/kg (approximately 2 and 10 times the maximum recommended human daily inhalation dose in adults and children, respectively, on a mcg/m2 basis) for 78 weeks or in rats at inhalation doses up to 57 mcg/kg (less than and equivalent to the maximum recommended human daily inhalation dose in adults and children, respectively, on a mcg/m2 basis) for 104 weeks.

Fluticasone propionate did not induce gene mutation in prokaryotic or eukaryotic cells in vitro . No significant clastogenic effect was seen in cultured human peripheral lymphocytes in vitro or in the mouse micronucleus test.

No evidence of impairment of fertility was observed in reproductive studies conducted in male and female rats at subcutaneous doses up to 50 mcg/kg (less than the maximum recommended human daily inhalation dose on a mcg/m2 basis). Prostate weight was significantly reduced at a subcutaneous dose of 50 mcg/kg.

Pregnancy

Teratogenic Effects

Pregnancy Category C. Subcutaneous studies in the mouse and rat at 45 and 100 mcg/kg, respectively (less than the maximum recommended human daily inhalation dose on a mcg/m2 basis), revealed fetal toxicity characteristic of potent corticosteroid compounds, including embryonic growth retardation, omphalocele, cleft palate, and retarded cranial ossification. No teratogenicity was seen in the rat at inhalation doses up to 68.7 mcg/kg (less than the maximum recommended human daily inhalation dose on a mcg/m2 basis).

In the rabbit, fetal weight reduction and cleft palate were observed at a subcutaneous dose of 4 mcg/kg (less than the maximum recommended human daily inhalation dose on a mcg/m2 basis). However, no teratogenic effects were reported at oral doses up to 300 mcg/kg (approximately 3 times the maximum recommended human daily inhalation dose on a mcg/m2 basis) of fluticasone propionate. No fluticasone propionate was detected in the plasma in this study, consistent with the established low bioavailability following oral administration (see CLINICAL PHARMACOLOGY: Pharmacokinetics: Absorption ).

Fluticasone propionate crossed the placenta following administration of a subcutaneous dose of 100 mcg/kg to mice (less than the maximum recommended human daily inhalation dose on a mcg/m2 basis), a subcutaneous or an oral dose of 100 mcg/kg to rats (less than the maximum recommended daily inhalation dose on a mcg/m2 basis), and an oral dose of 300 mcg/kg to rabbits (approximately 3 times the maximum recommended human daily inhalation dose on a mcg/m2 basis).

There are no adequate and well-controlled studies in pregnant women. FLOVENT HFA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Experience with oral corticosteroids since their introduction in pharmacologic, as opposed to physiologic, doses suggests that rodents are more prone to teratogenic effects from corticosteroids than humans. In addition, because there is a natural increase in corticosteroid production during pregnancy, most women will require a lower exogenous corticosteroid dose and many will not need corticosteroid treatment during pregnancy.

Nursing Mothers

It is not known whether fluticasone propionate is excreted in human breast milk. However, other corticosteroids have been detected in human milk. Subcutaneous administration to lactating rats of 10 mcg/kg tritiated fluticasone propionate (less than the maximum recommended human daily inhalation dose on a mcg/m2 basis) resulted in measurable radioactivity in milk.

Since there are no data from controlled trials on the use of FLOVENT HFA by nursing mothers, a decision should be made whether to discontinue nursing or to discontinue FLOVENT HFA, taking into account the importance of FLOVENT HFA to the mother.

Caution should be exercised when FLOVENT HFA is administered to a nursing woman.

Pediatric Use

The safety and effectiveness of FLOVENT HFA in children 12 years of age and older have been established (see CLINICAL PHARMACOLOGY: Pharmacokinetics: Special Populations: Pediatric, CLINICAL TRIALS: Pediatric Patients, ADVERSE REACTIONS: Pediatric Patients). Use of FLOVENT HFA in patients 4 to 11 years of age is supported by evidence from adequate and well-controlled studies in adults and adolescents 12 years of age and older, pharmacokinetic studies in patients 4 to 11 years of age, established efficacy of fluticasone propionate formulated as FLOVENT® DISKUS® (fluticasone propionate inhalation powder) and FLOVENT® ROTADISK® (fluticasone propionate inhalation powder) in patients 4 to 11 years of age, and supportive findings with FLOVENT HFA in a study conducted in patients 4 to 11 years of age. Types of adverse events in pediatric patients 4 to 11 years of age were generally similar to those observed in adults and adolescents.

Children Less Than 4 Years of Age

Pharmacokinetics

A 12-week, double-blind, placebo-controlled, parallel-group study was conducted in children with asthma aged 1 to <4 years. Population pharmacokinetics analyses were conducted in 164 children treated with 88 mcg of FLOVENT HFA administered twice daily with the AeroChamber Plus VHC with facemask. The predicted AUC0-τ and Cmax ranged from 58.30 to 923.90 pg•hr/mL with a median of 129.05 pg•hr/mL and from 15.71 to 85.13 pg/mL with a median of 20.30 pg/mL, respectively. Predicted geometric means for AUC0-τ and Cmax were 141 pg•hr/mL (95% CI: 127, 156) and 22 pg/mL (95% CI: 21, 23), respectively, indicating higher levels of exposure in children aged 1 to <4 years compared to those in children aged 4 to 11 years (see CLINICAL PHARMACOLOGY: Pharmacokinetics: Special Populations: Pediatric). Non-compartmental pharmacokinetic analyses in children aged 4 to 11 years showed AUC0-τ and Cmax ranged from not calculable to 322 pg•hr/mL with a median of 30.20 pg•hr/mL and from below the limit of quantitation (BLQ) to 87.4  pg/mL with median of 18.8 pg/mL, respectively when the same dosage of FLOVENT HFA was administered without the VHC and facemask.

In a study in children 6 to <12 months of age with reactive airways disease, plasma fluticasone propionate was measured over a 12-hour dosing period after 4 weeks of treatment with 88 mcg of FLOVENT HFA twice daily with an AeroChamber Plus VHC with facemask. The AUC0-τ and Cmax ranged from not calculable to 671.74 pg•hr/mL with a median of 104.2 pg•hr/mL and from BLQ to 106 pg/mL with a median of 32.0 pg/mL, respectively. The geometric means for AUC0-τ and Cmax were 75 pg•hr/mL (95% CI: 34, 166; N = 16) and 25 pg/mL (95% CI: 13, 45; N = 17), respectively. The geometric mean AUC0-τ and Cmax values in children 6 to <12 months of age were higher than those in children aged 4 to 11 years taking the same dosage of FLOVENT HFA without the VHC and facemask (see CLINICAL PHARMACOLOGY: Pharmacokinetics: Special Populations: Pediatric).

Population pharmacokinetic analysis of 102 male and 62 female subjects with asthma aged 1 to <4 years indicated that systemic exposure was not influenced by patient demographics, including gender. No overall differences in fluticasone propionate pharmacokinetics were observed between male and female patients with asthma.

Pharmacodynamics

A 12-week, double-blind, placebo-controlled, parallel-group study was conducted in children with asthma aged 1 to <4 years. Twelve-hour overnight urinary cortisol excretion after a 12-week treatment period with 88 mcg of FLOVENT HFA twice daily (n = 73) and with placebo (n = 42) were calculated. The mean and median change from baseline in urine cortisol over 12 hours were -0.7 and 0.0 mcg for FLOVENT HFA and 0.3 and -0.2 mcg for placebo treatments, respectively.

In a 1-way crossover study in children 6 to <12 months of age with reactive airways disease (N = 21), serum cortisol was measured over a 12-hour dosing period. Patients received placebo treatment for a 2-week period followed by a 4-week treatment period with 88 mcg of FLOVENT HFA twice daily with an AeroChamber Plus VHC with facemask. The geometric mean ratio of serum cortisol over 12 hours (AUC0-12 hr) following FLOVENT HFA (n = 16) versus placebo (n = 18) was 0.95 (95% CI: 0.72, 1.27).

Safety

FLOVENT HFA administered as 88 mcg twice daily has been evaluated for safety in 239 pediatric patients 1 to <4 years of age in a 12-week, double-blind, placebo-controlled study. Treatments were administered with an AeroChamber Plus VHC with facemask. In pediatric patients 1 to <4 years of age receiving FLOVENT HFA, the following events occurred with a frequency >3% and more frequently than in pediatric patients who received placebo, regardless of causality assessment: pyrexia, nasopharyngitis, upper respiratory tract infection, vomiting, otitis media, diarrhea, bronchitis, pharyngitis, and viral infection.

FLOVENT HFA administered as 88 mcg twice daily has also been evaluated for safety in 23 pediatric patients 6 to 12 months of age in an open-label placebo-controlled study. Treatments were administered with an AeroChamber Plus VHC with facemask for 2 weeks with placebo followed by 4 weeks with active drug. Adverse events after placebo and active drug were similar in kind and frequency.

In Vitro Testing of Dose Delivery With Holding Chambers

In vitro dose characterization studies were performed to evaluate the delivery of FLOVENT HFA via holding chambers with attached facemasks. The studies were conducted with 2 different holding chambers (AeroChamber Plus VHC and AeroChamber Z-STAT Plus™ VHC) and facemasks (small and medium size) at inspiratory flow rates of 4.9, 8.0, and 12.0 L/min in combination with holding times of 0, 2, 5, and 10 seconds. The flow rates were selected to be representative of inspiratory flow rates of children aged 6 to 12 months, 2 to 5 years, and over 5 years, respectively. The mean delivered dose of fluticasone propionate through the holding chambers with facemasks was lower than the 44 mcg of fluticasone propionate delivered directly from the actuator mouthpiece. The results were similar through both holding chambers (see Table 1 for data for the AeroChamber Plus VHC). The fine particle fraction (approximately 1 to 5 μm) across the flow rates used in these studies was 70% to 84% of the delivered dose, consistent with the removal of the coarser fraction by the holding chamber. In contrast, the fine particle fraction for FLOVENT HFA delivered without a holding chamber typically represents 42% to 55% of the delivered dose measured at the standard flow rate of 28.3 L/min. These data suggest that even at low flow rates and extended holding times potentially experienced in realistic situations with young children, an adequate amount of fluticasone propionate can be delivered to pediatric patients via a holding chamber and facemask at the recommended doses.

Table 1: In Vitro Medication Delivery Through AeroChamber Plus® Valved Holding Chamber With a Facemask

Age

Facemask

Flow

Rate

(L/min)

Holding

Time

(seconds)

Mean Medication

Delivery Through

AeroChamber

Plus VHC

(mcg/actuation)

Body

Weight

50th

Percentile

(kg)*

Medication

Delivered

per

Actuation

(mcg/kg)

6 to 12

Small

4.9

0

8.3

7.5-9.9

0.8-1.1

Months

2

6.7

0.7-0.9

5

7.5

0.8-1.0

10

7.5

0.8-1.0

2 to 5

Small

8.0

0

7.3

12.3-18.0

0.4-0.6

Years

2

6.8

0.4-0.6

5

6.7

0.4-0.5

10

7.7

0.4-0.6

2 to 5

Medium

8.0

0

7.8

12.3-18.0

0.4-0.6

Years

2

7.7

0.4-0.6

5

8.1

0.5-0.7

10

9.0

0.5-0.7

>5 Years

Medium

12.0

0

12.3

18.0

0.7

2

11.8

0.7

5

12.0

0.7

10

10.1

0.6

* Centers for Disease Control growth charts, developed by the National Center for Health Statistics in collaboration with the National Center for Chronic Disease Prevention and Health Promotion (2000). Ranges correspond to the average of the 50th percentile weight for boys and girls at the ages indicated.

A single inhalation of FLOVENT HFA in a 70-kg adult without use of a valved holding chamber and facemask delivers approximately 44 mcg, or 0.6 mcg/kg.

Orally inhaled corticosteroids may cause a reduction in growth velocity when administered to pediatric patients. A reduction of growth velocity in children or teenagers may occur as a result of poorly controlled asthma or from use of corticosteroids including inhaled corticosteroids. The effects of long-term treatment of children and adolescents with inhaled corticosteroids, including fluticasone propionate, on final adult height are not known.

Controlled clinical studies have shown that inhaled corticosteroids may cause a reduction in growth in pediatric patients. In these studies, the mean reduction in growth velocity was approximately 1 cm/year (range, 0.3 to 1.8 cm/year) and appears to depend upon dose and duration of exposure. This effect was observed in the absence of laboratory evidence of HPA axis suppression, suggesting that growth velocity is a more sensitive indicator of systemic corticosteroid exposure in pediatric patients than some commonly used tests of HPA axis function. The long-term effects of this reduction in growth velocity associated with orally inhaled corticosteroids, including the impact on final adult height, are unknown. The potential for “catch-up” growth following discontinuation of treatment with orally inhaled corticosteroids has not been adequately studied. The effects on growth velocity of treatment with orally inhaled corticosteroids for over 1 year, including the impact on final adult height, are unknown. The growth of children and adolescents receiving orally inhaled corticosteroids, including FLOVENT HFA, should be monitored routinely (e.g., via stadiometry). The potential growth effects of prolonged treatment should be weighed against the clinical benefits obtained and the risks associated with alternative therapies. To minimize the systemic effects of orally inhaled corticosteroids, including FLOVENT HFA, each patient should be titrated to the lowest dose that effectively controls his/her symptoms.

Since a cross study comparison in adolescent and adult patients (≥12 years of age) indicated that systemic exposure of inhaled fluticasone propionate from FLOVENT HFA would be higher than exposure from FLOVENT ROTADISK, results from a study to assess the potential growth effects of FLOVENT ROTADISK in pediatric patients (4 to 11 years of age) are provided.

A 52-week placebo-controlled study to assess the potential growth effects of fluticasone propionate inhalation powder (FLOVENT ROTADISK) at 50 and 100 mcg twice daily was conducted in the US in 325 prepubescent children (244 males and 81 females) aged 4 to 11 years. The mean growth velocities at 52 weeks observed in the intent-to-treat population were 6.32 cm/year in the placebo group (n = 76), 6.07 cm/year in the 50-mcg group (n = 98), and 5.66 cm/year in the 100-mcg group (n = 89). An imbalance in the proportion of children entering puberty between groups and a higher dropout rate in the placebo group due to poorly controlled asthma may be confounding factors in interpreting these data. A separate subset analysis of children who remained prepubertal during the study revealed growth rates at 52 weeks of 6.10 cm/year in the placebo group (n = 57), 5.91 cm/year in the 50-mcg group (n = 74), and 5.67 cm/year in the 100-mcg group (n = 79). In children 8.5 years of age, the mean age of children in this study, the range for expected growth velocity is: boys – 3rd percentile = 3.8 cm/year, 50th percentile = 5.4 cm/year, and 97th percentile = 7.0 cm/year; girls – 3rd percentile = 4.2 cm/year, 50th percentile = 5.7 cm/year, and 97th percentile = 7.3 cm/year.

The clinical significance of these growth data is not certain. Physicians should closely follow the growth of children and adolescents taking corticosteroids by any route, and weigh the benefits of corticosteroid therapy against the possibility of growth suppression if growth appears slowed. Patients should be maintained on the lowest dose of inhaled corticosteroid that effectively controls their asthma.

Geriatric Use

Of the total number of patients treated with FLOVENT HFA in US and non-US clinical trials, 173 were 65 years of age or older, 19 of which were 75 years of age or older. No apparent differences in safety or efficacy were observed between these patients and younger patients. No overall differences in safety were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic function and of concomitant disease or other drug therapy.

Page last updated: 2008-07-15

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