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SIDE EFFECTS
In controlled U.S. studies, more than 3300 patients with
seasonal allergic, perennial allergic, or perennial nonallergic
rhinitis received treatment with intranasal fluticasone
propionate. In general, adverse reactions in clinical
studies have been primarily associated with irritation
of the nasal mucous membranes, and the adverse reactions
were reported with approximately the same frequency by
patients treated with the vehicle itself. The complaints
did not usually interfere with treatment. Less than 2%
of patients in clinical trials discontinued because of
adverse events; this rate was similar for vehicle placebo
and active comparators.
Systemic corticosteroid side effects were not reported
during controlled clinical studies up to 6 months' duration
with fluticasone propionate nasal spray. If recommended
doses are exceeded, however, or if individuals are particularly
sensitive, or taking fluticasone propionate nasal spray
in conjunction with administration of other corticosteroids,
symptoms of hypercorticism e.g., Cushing's syndrome, could
occur.
The following incidence of common adverse reactions (>3%,
where incidence in fluticasone propionate-treated subjects
exceeded placebo) is based upon seven controlled clinical
trials in which 536 patients (57 girls and 108 boys aged
4 to 11 years, 137 female and 234 male adolescents and
adults) were treated with fluticasone propionate nasal
spray 200 mcg once daily over 2 to 4 weeks and two controlled
clinical trials in which 246 patients (119 female and
127 male adolescents and adults) were treated with fluticasone
propionate nasal spray 200 mcg once daily over 6 months
(see TABLE 1). Also included in the table are adverse
events from two studies in which 167 children (45 girls
and 122 boys aged 4 to 11 years) were treated with fluticasone
propionate nasal spray 100 mcg once daily for 2 to 4 weeks.
TABLE 1 Overall Adverse
Experiences with >3% Incidence on Fluticasone
Propionate in Controlled Clinical Trials with Fluticasone
Propionate Nasal Spray in Patients ³4 Years
with Seasonal or Perennial Allergic Rhinitis |
| |
|
Fluticasone Propionate Nasal
Spray Once Daily |
| |
Vehicle Placebo |
100 mcg |
200 mcg |
| |
(n=758) % |
(n=167) % |
(n=782) % |
| Headache |
14.6 |
6.6 |
16.1 |
| Pharyngitis |
7.2 |
6.0 |
7.8 |
| Epistaxis |
5.4 |
6.0 |
6.9 |
| Nasal burning/nasal irritation |
2.6 |
2.4 |
3.2 |
| Nausea/vomiting |
2.0 |
4.8 |
2.6 |
| Asthma symptoms |
2.9 |
7.2 |
3.3 |
| Cough |
2.8 |
3.6 |
3.8 |
Other adverse events that occurred in £3% but ³1%
of patients and that were more common with fluticasone
propionate (with uncertain relationship to treatment)
included: blood in nasal mucus, runny nose, abdominal
pain, diarrhea, fever, flu-like symptoms, aches and pains,
dizziness, bronchitis.
Observed During Clinical Practice:
In addition to adverse events reported from clinical trials,
the following events have been identified during postapproval
use of fluticasone propionate in clinical practice. Because
they are reported voluntarily from a population of unknown
size, estimates of frequency cannot be made. These events
have been chosen for inclusion due to either their seriousness,
frequency of reporting, causal connection to fluticasone
propionate, occurrence during clinical trials, or a combination
of these factors.
General: Hypersensitivity reactions,
including angioedema, skin rash, edema of the face and
tongue, pruritus, urticaria, bronchospasm, wheezing, dyspnea,
and anaphylaxis/anaphylactoid reactions, which in rare
instances were severe.
Ear, Nose, and Throat: Alteration
or loss of sense of taste and/or smell and, rarely, nasal
septal perforation, nasal ulcer, sore throat, throat irritation
and dryness, cough, hoarseness, and voice changes.
Eye: Dryness and irritation,
conjunctivitis, blurred vision, glaucoma, increased intraocular
pressure, and cataracts.
DRUG INTERACTIONS
In a placebo-controlled, crossover study in eight healthy
volunteers, coadministration of a single dose of orally
inhaled fluticasone propionate (1000 mcg, 5 times the
maximum daily intranasal dose) with multiple doses of
ketoconazole (200 mg) to steady state resulted in increased
mean fluticasone propionate concentrations, a reduction
in plasma cortisol AUC, and no effect on urinary excretion
of cortisol. This interaction may be due to an inhibition
of the cytochrome P450 3A4 isoenzyme system by ketoconazole,
which is also the route of metabolism of fluticasone propionate.
No drug interaction studies have been conducted with fluticasone
propionate nasal spray; however, care should be exercised
when fluticasone propionate is coadministered with long-term
ketoconazole and other known cytochrome P450 3A4 inhibitors.
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