ADVERSE REACTIONS
In the controlled clinical trials, adverse events were monitored in the 161 patients who used TRI-LUMA® Cream once daily during an 8-week treatment period. There were 102 (63%) patients who experienced at least one treatment-related adverse event during these studies. In the long-term clinical study, from a total of 314 patients treated with TRI-LUMA® Cream for at least 180 cumulative days, there were 202 (64%) patients who experienced at least one treatment-related adverse event. No significant increase in severity or incidence of the adverse events was observed from long term use of TRI-LUMA® Cream compared with events reported during the 8-week controlled clinical studies. The most frequently reported adverse events that were observed from the controlled clinical trials and the long term safety were erythema, desquamation, and burning, at the site of application. The number and percentages of these events were markedly lower in the long-term study than in the controlled clinical studies. The great majority of these events were mild to moderate in severity.
Adverse events reported by at least 1% of patients and judged by the investigators to be reasonably related to treatment with TRI-LUMA® Cream from the controlled clinical studies and the long-term study are summarized (in decreasing order of frequency).
| Incidence and Frequency of Treatment-related Adverse Events with TRI-LUMA Cream in at least 1% or more of Patients (N=161) |
| Adverse Event |
Number (%) of Patients |
|
Erythema
|
66 (41%) |
|
Desquamation
|
61 (38%) |
|
Burning
|
29 (18%) |
|
Dryness
|
23 (14%) |
|
Pruritus
|
18 (11%) |
|
Acne
|
8 (5%) |
|
Paresthesia
|
5 (3%) |
|
Telangiectasia
|
5 (3%) |
|
Hyperesthesia
|
3 (2%) |
|
Pigmentary changes
|
3 (2%) |
|
Irritation
|
3 (2%) |
|
Papules
|
2 (1%) |
|
Acne-like rash
|
1 (1%) |
|
Rosacea
|
1 (1%) |
|
Dry Mouth
|
1 (1%) |
|
Rash
|
1 (1%) |
|
Vesicles
|
1 (1%) |
|
In an open-label long-term safety study, patients who have had cumulative treatment of melasma with TRI-LUMA® Cream for 6 months showed a similar pattern of adverse events as in the 8-week studies.
Summary of Most Common Treatment-Related Adverse Events
(TRAE) a Study 29 |
| Preferred Term |
Number (%) of Patients Treatment Group
TRI-LUMA® |
| All Patients (N=569) |
Patients with at least 180 Cumulative Days of TRI-LUMA® Treatment Days (N=314) |
|
Total number of TRAE a |
326 (57.29) |
202 (64.33) |
|
Application site erythema
|
166 (29.17) |
105 (33.44) |
|
Application site desquamation
|
145 (25.48) |
91 (28.98) |
|
Application site dryness
|
46 (8.08) |
27 (8.60) |
|
Application site burning
|
38 (6.68) |
25 (7.96) |
|
Application site inflammation
|
31 (5.45) |
24 (7.64) |
|
Application site reaction nos
|
31 (5.45) |
17 (5.41) |
|
Application site rash
|
30 (5.27) |
18 (5.73) |
|
Application site pruritus
|
24 (4.22) |
18 (5.73) |
|
Application site pigmentation changes
|
23 (4.04) |
18 (5.73) |
a Defined as "probably" or "possibly" related to study medication
Data source: Section 14.3, Tables 8.1.1, 8.1.2, and 8.1.3
|
|
The severity, incidence and type of adverse events experienced from 6 months cumulative use were not significantly different from the events reported for all patients.
The incidence of application site pigmentation changes that occurred in both the controlled and long-term safety studies included 11 occurrences of hypopigmentation and 18 occurrences of hyperpigmentation in 27 patients.
The following local adverse reactions have been reported infrequently with topical corticosteroids. They may occur more frequently with the use of occlusive dressings, especially with higher potency corticosteroids. These reactions are listed in an approximate decreasing order of occurrence: burning, itching, irritation, dryness, folliculitis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, skin atrophy, striae, and miliaria.
TRI-LUMA® Cream contains hydroquinone, which may produce exogenous ochronosis, a gradual blue-black darkening of the skin, whose occurrence should prompt discontinuation of therapy.
Cutaneous hypersensitivity to the active ingredients of TRI-LUMA® Cream has been reported in the literature. In a patch test study to determine sensitization potential in 221 healthy volunteers, three volunteers developed sensitivity reactions to TRI-LUMA® Cream or its components.
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