The prescribing information for Tri-Luma (fluocinolone acetonide 0.01%, hydroquinone 4%, tretinoin 0.05%, per its Drugs@FDA record) reports that in its controlled clinical trials, 102 (63%) of the 161 subjects who used the cream once daily during an 8-week treatment period experienced at least one treatment-related adverse event. This guide sets out the figures and warnings that labels and trials report, and what the sources say to do.
What the Tri-Luma label reports
The Tri-Luma label (fluocinolone acetonide 0.01%, hydroquinone 4%, tretinoin 0.05%) says the most frequently reported events were erythema, desquamation, burning, dryness, and pruritus at the site of application, and that the majority of these events were mild to moderate in severity. It also says the cream contains hydroquinone and tretinoin that may cause mild to moderate irritation. Table 1 of the label lists treatment-related adverse events in at least 1% or more of subjects (N=161):
| Event | Subjects, n (%) |
|---|---|
| Erythema | 66 (41%) |
| Desquamation | 61 (38%) |
| Burning | 29 (18%) |
| Dryness | 23 (14%) |
| Pruritus | 18 (11%) |
| Acne | 8 (5%) |
Longer use and trial comparisons
The Tri-Luma label (fluocinolone acetonide 0.01%, hydroquinone 4%, tretinoin 0.05%) also says that in an open-label trial, subjects who had cumulative treatment of melasma with the cream for 6 months showed a similar pattern of adverse events as in the 8-week studies. A long-term, multicenter, open-label study of once-daily Tri-Luma triple combination cream (fluocinolone acetonide 0.01%, hydroquinone 4%, tretinoin 0.05%) in patients with facial melasma, with no comparison group described, reported that 129 patients (57%) experienced at least one treatment-related adverse event. It described most as expected application-site reactions that were mild and transient. A study without a comparison group cannot show cause and effect.
Randomized trials report side effects for hydroquinone 4% cream as a comparator:
- In a randomized trial in Asian patients with melasma, a fixed triple combination (fluocinolone acetonide 0.01%, hydroquinone 4%, tretinoin 0.05%) was compared with hydroquinone 4% cream. Related adverse events occurred in 63/129 (48.8%) on the triple combination and 18/131 (13.7%) on hydroquinone, but most were mild and none was severe.
- In a double-blind randomized split-face trial of niacinamide 4% against hydroquinone 4% for eight weeks in twenty-seven patients, side effects were present in 18% with niacinamide versus 29% with hydroquinone.
- In a small double-blind randomized split-face trial of 5% ascorbic acid against 4% hydroquinone in sixteen women with idiopathic melasma, used at night for 16 weeks, side-effects were present in 68.7% (11/16) with hydroquinone versus 6.2% (1/16) with ascorbic acid.
These trials used different creams, groups and methods. Their figures should not be compared across trials or used to rank products.
Allergy and hypersensitivity warnings
The Tri-Luma prescribing information (fluocinolone acetonide 0.01%, hydroquinone 4%, tretinoin 0.05%) lists a history of hypersensitivity to the product or any of its components as a contraindication. Its hypersensitivity warning says the cream contains sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening asthmatic episodes in susceptible individuals.
The adverse reactions section of a prescription hydroquinone 4% cream label lists dryness and fissuring of paranasal and infraorbital areas, erythema, and stinging as reactions that have been reported, without giving percentages. It also says occasional hypersensitivity (localized contact dermatitis) may develop, and that if this occurs the medication should be discontinued and the physician notified immediately.
What the sources say to do
The patient leaflet for Tri-Luma (fluocinolone acetonide 0.01%, hydroquinone 4%, tretinoin 0.05%) says to stop using the cream and call a doctor to get medical help right away for symptoms including swelling of the face, eyes, lips, tongue, or throat, trouble breathing, severe itching, skin rash or hives, or change in skin color. It also says to stop using the cream and tell a doctor if a blue-black darkening of the skin develops. The FDA Skin Facts! page says that anyone who experiences a bad reaction from the use of a skin product should contact their health care provider.
What this does not tell you
The sources used here report no trial of hydroquinone 8% or of the four-ingredient blend with tretinoin, niacinamide and vitamin C, so findings at 4% or in other combinations cannot be assumed to apply. The Tri-Luma figures describe a cream with three active ingredients and cannot be split by ingredient. The adverse reactions section of the 4% cream label gives no percentages. A licensed provider decides what any of this means for a person.