Triamcinolone Acetonide

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Abstract
Triamcinolone acetonide is a synthetic glucocorticoid which has been formulated as both an aerosol and an aqueous mete red-dose pump spray for nasal inhalation in the treatment of allergic rhinitis. Nasally administered triamcinolone acetonide is not significantly absorbed into the systemic circulation and does not suppress hypothalamic-pituitary-adrenal (HPA) axis function at therapeutic dosages. Clinical trials with either formulation have shown that once-daily triamcinolone acetonide 110 to 220µg reduces symptoms of allergic rhinitis within the first day of administration. Once symptoms are under control, the dosage of aqueous triamcinolone acetonide may be reduced from 220 to 110 µg/day without loss of effect. Both aqueous and aerosol formulations of triamcinolone acetonide are significantly more effective in relieving symptoms and reducing nasal eosinophil influx than placebo. Once-daily intranasal triamcinolone acetonide 220 µg/day produced similar reductions from baseline in nasal symptoms of allergic rhinitis, when measured both subjectively (visual analogue scales) and objectively (anterior rhinomanometry), to those seen with beclomethasone 84 to 168µg twice daily, fluticasone 200µg once daily or flunisolide 100∥ twice daily for 3 to 12 weeks. Furthermore, triamcinolone acetonide aerosol 220 µg/day was significantly more effective at reducing the nasal symptoms of allergic rhinitis than the oral antihistamines loratadine and astemizole (both 10mg daily) and was equally as effective in reducing the associated ocular symptoms. The use of intranasal triamcinolone acetonide and oral loratadine in combination did not confer any additional advantage over triamcinolone acetonide alone. Triamcinolone acetonide [110 to either 220 µg/day (aqueous) or 440 µg/day (aerosol)] was well tolerated in clinical trials; headache and epistaxis were the only adverse events considered possibly or probably related to aerosol therapy in a 1-year study (110 to 440 µg/day). Therefore, in accordance with the recommendations from the International Rhinitis Management Working Group regarding the use of nasal glucocorticoids, triamcinolone acetonide may be considered a first-line therapy option in adults with moderately severe seasonal allergic rhinitis with predominantly nasal symptoms and also in children and adult patients with perennial allergic rhinitis. In patients with allergic rhinitis, intranasal triamcinolone acetonide aerosol 220 µg/day, compared with placebo, had no effect on histamine or tryptase levels in nasal exudate, but attenuated albumin levels and significantly reduced nasal eosinophil infiltration. Response of both upper and lower airways to controlled allergen exposure was also reduced in patients who received triamcinolone acetonide aerosol 440 µg/day. In addition, triamcinolone acetonide aerosol 440 µg/day compared with placebo reduced nasal ragweed-specific IgE and attenuated the seasonal increase in specific serum IgE in patients with ragweed allergy. The symptoms of allergic rhinitis, including those associated with the early phase inflammatory response, were reduced by intranasal triamcinolone acetonide (440 µg/day) within 1 day of starting therapy. Unlike prednisone 10 mg/day, aqueous (220 µg/day) and aerosol (440 µg/day) formulations of triamcinolone acetonide once daily for 6 weeks had no effect on adrenocortical function in adults with rhinitis. Similarly, no effect was seen with the aqueous formulation 220 to 440 µg/day in a noncomparative trial in children. After a single dose of intranasal triamcinolone acetonide aerosol 440µg, pharmacokinetic parameters were similar in patients with allergy and nonallergic volunteers. This suggests that nasal inflammation does not enhance the minimal systemic absorption of triamcinolone acetonide aerosol. After 440 µg/day for 6 weeks, maximum plasma drug concentration (Cmax) was 0.40 µg/L, time to Cmax (tmax) was 4.0 hours, area under the plasma concentration-time curve from 0 to 12 hours (AUC12) was 2.0 µg/L · h and elimination half-life (t1/2p) was 3.3 hours in 4 patients with allergy. Accumulation was not apparent with continuous use of triamcinolone acetonide aerosol for up to 6 weeks. In 24 patients and 24 volunteers, Cmax values were dose-dependent and greater at all 3 dose levels (110, 220 and 440µg; 0.25 to 0.82 µg/L) with the aqueous than with the aerosol (440µg; 0.14 to 0.16 µg/L) formulation; again, there was little difference between values recorded in patients and volunteers. The AUC∞ values were also dose-dependent and, with the exception of the AUC after a dose of 110µg in volunteers, were greater after the administration of the aqueous formulation (1.45 to 4.68 jug/L · h) than after the aerosol formulation (1.31 to 1.70 µg/L · h). Mean tmax values after aqueous administration were 1.3 to 1.8 hours for all recipients, and after aerosol administration were 2.9 and 4.5 hours for patients and volunteers, respectively (no statistical analysis reported). Mean t1/2β values of 4.9 hours (patients) and 5.3 hours (volunteers) were observed after aerosol administration, in comparison with 3.1 to 3.3 hours for all recipients after the administration of the aqueous formulation (no statistical analysis reported). Positron emission tomography and magnetic resonance imaging scans demonstrated that 11C-triamcinolone acetonide migrated further into the nasal passages after initial deposition in the anterior of the nose. About 4% of a 110µg dose of the aqueous thixotropic formulation of 11C-triamcinolone acetonide was distributed to the maxillary and frontal sinuses within 30 seconds of administration. Most of the agent (maximum 64%) was distributed to the turbinate region. Target tissues (frontal cavity, sinuses and turbinates) retained up to 16% of the dose after 2 hours. Up to 83% of the total dose was directly deposited on the target tissues. Once-daily administration of intranasal triamcinolone acetonide (either aqueous or aerosol formulation) provides effective relief of allergic rhinitis symptoms (congestion, rhinorrhoea and sneezing). Aqueous or aerosol intranasal triamcinolone acetonide 220 µg/day, compared with placebo, significantly improved the symptoms of allergic rhinitis within 1 day of initial administration. Efficacy was generally maintained for the duration of therapy (up to 1 year). Moreover, reductions in symptom scores from baseline after 1 week of therapy were maintained for up to 2 weeks after halving the daily aqueous triamcinolone acetonide dose from 220 to 110µg. Ocular symptoms were also significantly reduced from baseline assessments in triamcinolone acetonide recipients compared with those receiving placebo. In general, patient and physician global efficacy assessments favoured triamcinolone acetonide over placebo. Beneficial effects of intranasal triamcinolone acetonide on symptoms of allergic rhinitis were also observed in adolescents (aged 11 to 17 years) and children (aged 4 to 12 years) who received either formulation of the agent at dosages of 82.5 to 220 µg/day for 2 to 12 weeks. Comparison of oral (275 µg/day) and intranasal (220 µg/day; aqueous) triamcinolone acetonide suggests that the efficacy of the drug in the treatment of rhinitis is achieved primarily by topical contact, since neither placebo nor oral triamcinolone acetonide improved nasal symptoms. Symptoms were significantly suppressed in patients with seasonal allergic rhinitis who received triamcinolone acetonide aerosol 220µg once daily compared with those who received placebo for at least 1 week before the onset of the pollen season. When compared with other nasally administered corticosteroids, once-daily intranasal triamcinolone acetonide aerosol 220µg produced similar reductions from baseline evaluations of allergic rhinitis symptoms to those seen with beclomethasone aqueous formulation 84, 166 or 168 µg/day twice daily for up to 12 weeks, fluticasone 200µg once daily for 3 weeks or flunisolide `00µg twice daily for 4 weeks. In addition, intranasal triamcinolone acetonide aerosol 220µg provided relief from both nasal and ocular symptoms of rhinitis which was greater than or equal to that obtained with loratadine or astemizole (both 10 mg/day). The reduction in overall nasal index (sum of individual rhinitis scores) was greater (p < 0.01) in patients receiving triamcinolone acetonide (50% reduction in score) than astemizole (37%), but ocular symptoms were similarly reduced by about 40% from baseline in patients receiving triamcinolone acetonide, loratadine or astemizole. Physician global assessment favoured triamcinolone acetonide over oral antihistamine therapy. In one double-blind study (n=229), the combined use of intranasal triamcinolone acetonide and oral loratadine did not confer additional therapeutic benefits compared with triamcinolone acetonide alone. Adverse events considered possibly or probably related to therapy in clinical trials included nasal irritation, sneezing, dry mucous membranes, nasosinus discomfort, throat discomfort, headache and epistaxis. However, in a 1 -year study of the aerosol formulation 110 to 440 µg/day, only headache (n=1) and epistaxis (n=5) were considered possibly or probably related to the medication in a study population of 93 patients. In a second study, an oral fungal infection (no further details given) was reported in 1 patient receiving nasally inhaled triamcinolone acetonide aqueous formulation 220 µg/day for 15 days. The concentration, formulation and frequency of application of intranasal triamcinolone acetonide did not appear to affect the incidence or type of adverse events reported. Triamcinolone acetonide for intranasal administration is available in aerosol and aqueous formulations; both supply 55µg of active compound per actuation. The recommended initial triamcinolone acetonide dosage for adults and children ≥6 years of age is 220 µg/day given as 2 actuations per nostril once daily. Efficacy should be assessed after 4 to 7 days. If necessary, in adults and children ≥ 12 years of age the dosage of the aerosol formulation may be increased to 440µg once daily or as a divided dose up to 4 times daily. In children 6 to 11 years of age the recommended initial (and maximum) once-daily dosage of the aerosol formulation is 220µg. The maximum recommended dosage for the aqueous formulation (adults only) is also 220µg once daily. With both formulations, dosage should be gradually reduced to 110 µg/day once symptoms are satisfactorily controlled. Patients changing from systemic to topical corticosteroids should be monitored, especially those who have received long term systemic corticosteroid therapy. The FDA advises that caution is required with use of triamcinolone acetonide (as with all other inhaled steroids) in patients with untreated infections (including quiescent tuberculosis), and those who have recently had nasal surgery and/or nasal septal ulcers.