Metronidazole 0.75% gel vs. ketoconazole 2% cream in the treatment of facial seborrheic dermatitis: a randomized, double-blind study

BACKGROUND: Recently, two placebo-controlled studies have shown that topical metronidazole was effective in the treatment of seborrheic dermatitis. OBJECTIVE: To compare the efficacy and safety of metronidazole 0.75% gel with that of ketoconazole 2% cream in the treatment of facial seborrheic dermatitis. METHODS: A total of 60 consecutive patients with facial seborrheic dermatitis were included. Patients were randomized into two groups. One group used ketoconazole 2% cream with metronidazole gel as vehicle; the other group used metronidazole 0.75% gel with ketoconazole cream as vehicle for a 4-week treatment period. Main outcome measures were change in clinical severity scores, patients' and investigator's global evaluation of improvement and frequency of side-effects. RESULTS: All the assessments were made by an investigator who was unaware of which group the patients were allocated to. Mean percentage decrease in clinical severity scores from baseline to last available visit was 63.4% (95% CI 57.7-69) and 54.4% (95% CI 47.9-61) in the ketoconazole- and metronidazole-treated patients, respectively (P = 0.31). Eighty-two per cent of patients in the ketoconazole group vs. 79% of patients in the metronidazole group rated their global improvement as significant or moderate (P > 0.05). No statistically significant difference in the frequency of side-effects was detected between the two groups. The results of this study need to be confirmed in further studies involving large numbers of patients. CONCLUSION: Our data demonstrated that metronidazole 0.75% gel had a comparable efficacy and safety profile with that of ketoconazole 2% cream in the treatment of facial seborrheic dermatitis.     

Permethrin 5% cream versus metronidazole 0.75% gel for the treatment of papulopustular rosacea. A randomized double-blind placebo-controlled study

BACKGROUND: Permethrin 5% cream used against human ectoparasites suggests that it may be effective in papulopustular rosacea. METHODS: This study included 63 patients diagnosed as having papulopustular rosacea based on the clinical and histological findings. Patients were randomly assigned into permethrin (n = 23), metronidazole (n = 20) and placebo (n = 20) groups. Scores of erythema, telangiectasia, edema and rhinophyma and the numbers of papules, pustules, inflammatory nodules and Demodex folliculorum were determined. Twenty-three patients were given permethrin 5% cream (Zalvor 5% skin cream, 20 patients metronidazole 0.75% gel (Roza gel and 20 patients placebo cream (Basis cream, in packages looking identical to those of metronidazole and permethrin creams, and were recommended to apply them to their faces twice a day. All patients were also given SPF 20 cream for protection against sunlight. Two months of treatment were planned, and the patients were invited to the clinic for fortnightly controls. Scores of erythema, telangiectasia, edema and rhinophyma and the numbers of papules, pustules, inflammatory nodules and D. folliculorum were recorded at each visit. The mean scores of erythema and the mean numbers of papules, pustules and D. folliculorum were determined at baseline and on days 15, 30, 45 and 60. Side effects were also detected. RESULTS: The effect of permethrin 5% cream on D. folliculorum was superior to that of metronidazole 0.75% gel. The effect of permethrin 5% cream on erythema and papules was found to be more effective than placebo and as effective as metronidazole 0.75% gel. However, it had no effect on telangiectasia, rhinophyma and pustules. CONCLUSION: It can be concluded that the application of permethrin 5% cream twice daily for 2 months can be as effective and reliable as metronidazole in the treatment of rosacea and a greater benefit can be gained when it is combined with other systemic and/or topical treatments.     

Refractory Demodex folliculitis in five children with acute lymphoblastic leukemia

We report five children with acute lymphocytic leukemia on maintenance chemotherapy who had Demodex folliculitis. None experienced complete clearing when treated with permethrin 5% cream. Topical metronidazole helped to lessen the eruption in four, but did not provide full clearing. The one child who was treated with sodium sulfacetamide 10%, sulfur 5% formulation had resolution of the eruption. We suggest that treatment of Demodex folliculitis in children with acute lymphocytic leukemia is more difficult than is suggested in the literature. Newer sodium sulfacetamide/sulfur formulations should be considered when treating this condition, particularly in children with acute lymphocytic leukemia.     

Once-daily topical metronidazole cream formulations in the treatment of the papules and pustules of rosacea

BACKGROUND: The papules and pustules of rosacea can be effectively treated with topical metronidazole. The optimal concentrations of metronidazole and optimum frequencies of application are uncertain. Traditionally, twice-daily applications have been advised, based on the pharmacokinetic profile of metronidazole. Once-daily applications may be safer and less expensive, and they may enhance patient compliance. OBJECTIVE: We compared the efficacy and safety of 2 commercially available topical metronidazole formulations (0.75% metronidazole cream formulation and 1.0% metronidazole cream formulation) when both were used in a once-daily regimen. METHODS: A multicenter, randomized, investigator-blind, parallel group trial was conducted at 3 separate clinical sites located in 3 US cities. The study enrolled 72 rosacea patients with at least 8 to 50 inflammatory facial lesions (pustules and papules) and moderately severe facial erythema. Patients were randomly assigned to receive either 0.75% metronidazole cream or 1.0% metronidazole cream and instructed to apply the medication once daily for 12 weeks. Patients' lesions were evaluated at baseline and at weeks 3, 6, 9, and 12. RESULTS: There were no significant differences between treatment groups for any of the efficacy parameters evaluated. The overall median percentage change in lesion count at end point for patients in the 0.75% metronidazole cream treatment group was -62% compared with -60% for the 1.0% metronidazole cream treatment group. The overall percentage change in erythema scores at endpoint for patients in the 0.75% metronidazole cream treatment group was -26% compared with -30% for patients in the 1.0% metronidazole cream treatment group. Regarding physician assessment of global severity, 57% of subjects (20/35) in the 0.75% metronidazole cream group compared with 37% of subjects (13/35) in the 1.0% metronidazole cream group were rated as having a clear to mild condition at end point. Both drugs were well tolerated; there was no significant difference in the number of drug-related adverse events between the two agents. CONCLUSION: This controlled trial demonstrates that both 0.75% metronidazole cream and 1.0% metronidazole cream, when used once daily, provide well-tolerated efficacy for moderate to severe rosacea.     

A comparison of topical azelaic acid 20% cream and topical metronidazole 0.75% cream in the treatment of patients with papulopustular rosacea

Background: Although it is important for physicians to have sufficient clinical data on which to base treatment decisions, little comparative data exist regarding newer treatment modalities for rosacea. Objective: The goal of the study was to compare the efficacy and safety of topical azelaic acid 20% cream and topical metronidazole 0.75% cream in the treatment of patients with papulopustular rosacea. Parameters of patient satisfaction to treatment were also assessed. Methods: Forty patients with the clinical manifestation of symmetric facial rosacea were investigated in this single-center, double-blind, randomized, contralateral split-face comparison clinical trial. Results: After 15 weeks of treatment, both azelaic acid and metronidazole induced significant, albeit equal reductions in the number of inflammatory lesions (pustules and papules). A significantly higher physician rating of global improvement was achieved with azelaic acid. Changes in the rosacea signs and symptoms of dryness, burning, telangiectasia, and itching were equal between treatments. A reduction in erythema tended toward significance with azelaic acid at week 15. A trace amount of stinging on application was noted with azelaic acid; however, such discomfort did not appear to concern patients because their overall impression of azelaic acid was superior to that of metronidazole. Conclusion: Azelaic acid 20% cream provides an effective and safe alternative to metro-nidazole 0.75% cream with the added benefit of increased patient satisfaction. (J Am Acad Dermatol 1999;40:961-5.)     

Improvement in pruritus in children with atopic dermatitis using pimecrolimus cream 1%

The objective of this study was to assess time to onset of pruritus improvement in a pediatric population treated with pimecrolimus cream 1%. This 8-day, double-blinded, vehicle-controlled study randomized 174 children and adolescents (aged 2-17 years) with mild to moderate atopic dermatitis (AD) and moderate to severe pruritus to twice-daily applications of pimecrolimus cream 1% or vehicle. There were no significant between-group differences in demographics or baseline disease characteristics. Pruritus was assessed by subjects using a 4-point pruritus severity scale (0-3). The primary efficacy variable was time to a 1 point or more improvement in pruritus score from baseline. The 2 treatment groups were compared using log-rank testing of the time-to-event data. In the per-protocol (PP) population, median times to a 1 point or more improvement in pruritus score were 48 and 72 hours for pimecrolimus and vehicle groups, respectively (P = .038). From day 3 onward, significantly more subjects (P = .023) in the pimecrolimus group versus the vehicle group reported complete pruritus resolution. Pimecrolimus cream 1% improved pruritus within 48 hours in children and adolescents with mild to moderate AD and achieved complete resolution of pruritus in a significantly greater number of subjects in the pimecrolimus group versus the vehicle group by the end of the 7-day treatment period (P = .008).     

A comparison of metronidazole 1% cream and pimecrolimus 1% cream in the treatment of patients with papulopustular rosacea: a randomized open‐label clinical trial

Background. There are various treatment options available for rosacea, depending on the subtype, but treatment is still generally unsatisfactory. Some reports have indicated beneficial effects of topical pimecrolimus. Aim. To compare the efficacy and safety of pimecrolimus 1% cream and metronidazole 1% cream in the treatment of patients with papulopustular rosacea (PR). Methods. A group of 49 patients with PR was investigated in this single‐centre, randomized, open‐label study. Patients were randomly assigned treatment with either pimecrolimus 1% cream or metronidazole 1% cream for 12 weeks. Response was evaluated by the inflammatory lesion count, the severity of facial erythema and telangiectasia, Physician’s Global Assessment (PGA), and safety and tolerability at baseline and at weeks 3, 6, 9 and 12. Results. In total, 48 patients completed the study. Both treatments were very effective in the treatment of PR. There were no significant differences between the treatments in inflammatory lesion counts, overall erythema severity scores and PGA evaluated from baseline to week 12 (P > 0.05). Neither treatment produced any clinically relevant improvement in telangiectasia. Conclusion. Pimecrolimus cream is no more efficacious than metronidazole cream in the treatment of PR.     

A double-blind study of 1% metronidazole cream versus systemic oxytetracycline therapy for rosacea

In a randomized double-blind trial fifty-one patients with rosacea were treated for 2 months with either 1% metronidazole cream and placebo tablets or with 250 mg oxytetracycline tablets taken twice daily, and placebo cream (the cream base). The patients were assessed before and at the end of the trial, using the following criteria: (1) overall clinical assessment, (2) lesion counts, (3) degree of erythema, (4) independent photographic evaluation, (5) patients' opinion. An improvement was shown in 90% of the patients of both groups, and there was no significant difference between the two treatments. One per cent metronidazole cream has been shown to be significantly better than a placebo cream in the treatment of rosacea (Gamborg Nielsen, 1983a), It was therefore considered important to compare the cream with conventional therapy, and for this reason a double-blind study of 1% metronidazole cream versus a daily dose of 500 mg oxytetracycline was performed.     

Cumulative irritation potential of adapalene 0.1% cream and gel compared with tazarotene cream 0.05% and 0.1%

Despite the many beneficial effects of dermatologic applications, most of the current treatments for acne cause local irritation. The objective of this study was to compare the ability of the epidermis to tolerate adapalene 0.1% cream and gel and tazarotene cream in concentrations of 0.05% and 0.1%. A total of 30 subjects were enrolled in the study. The test products were applied under occlusive dressings at randomized sites on the upper back for approximately 24 hours, 4 times a week, and for 72 hours, once a week, for a period of 3 weeks. Skin reactions (erythema score plus other local reactions) at the product application sites were assessed 15 to 30 minutes after dressing removal. Twenty-six subjects completed the study. A total of 16 subjects discontinued use of 1 or more of the test products because of irritation scores reaching severe or greater; all but one of these discontinuations were at sites treated with the tazarotene products. The mean 21-day cumulative irritancy indices for adapalene 0.1% cream and gel were significantly lower (P=.05) than those for tazarotene cream 0.05% and 0.1% and not notably higher than that of the negative control product.     

Cumulative irritation potential among metronidazole gel 1%, metronidazole gel 0.75%, and azelaic acid gel 15%

Topical therapy for rosacea aims to reduce inflammatory lesions and decrease erythema but can carry side effects such as stinging, pruritus, and burning. Metronidazole and azelaic acid gel 15% are U.S. Food and Drug Administration-approved for the treatment of rosacea. The current study was conducted to assess the cumulative irritation potential of 2 formulations of metronidazole 0.75% gel and 1% gel--and azelaic acid gel 15% over 21 days (N=36). Results of this study demonstrated a significantly greater poten tial for irritation from azelaic acid compared with metronidazole gel 0.75% (P < .0001), which had significantly greater potential for irritation compared with metronidazole gel 1% (P = .0054). Metronidazole gel 1% had a similar profile to white petrolatum.     

Short-course therapy with imiquimod 5% cream for solar keratoses: a randomized controlled trial

A dual-centre, randomized, double-blind, vehicle-controlled study was conducted to evaluate the safety and efficacy of short courses of therapy with imiquimod 5% cream in clearing >/=75% of baseline solar keratoses (SK) within a field of treatment. Subjects with 5-15 baseline SK within one treatment area (scalp, forehead and temples, or both cheeks) were randomized to apply imiquimod or vehicle cream to the entire treatment area three times a week for 3 weeks. Subjects were assessed 4 weeks after completing the first course for clearance of lesions. Subjects with <75% clearance were commenced on a second 3-week course of study cream. Subjects with >/=75% clearance were followed up until study completion without further therapy. All subjects were evaluated at the study endpoint of 14 weeks after initiating therapy for assessment of the primary outcome (>/=75% clearance of baseline solar keratoses). Twenty-one out of 29 (72%) imiquimod-treated subjects cleared >/=75% of baseline lesions compared with 3/10 (30%) subjects using the vehicle cream (Fisher's exact test, P = 0.027). Imiquimod was well tolerated. The present study has a short follow-up endpoint, but suggests that imiquimod is a potential therapeutic alternative in patients with SK.     

Medication formulation affects quality of life: a randomized single-blind study of clobetasol propionate foam 0.05% compared with a combined program of clobetasol cream 0.05% and solution 0.05% for the treatment of psoriasis

For topical medications commonly used to treat dermatologic conditions, outcomes may be affected by the choice of delivery vehicles. The aim of this study was to compare quality of life (QOL), effectiveness, user satisfaction, and cost-effectiveness of 2 clobetasol regimens for the treatment of psoriasis over 14 days. In a single-blind design, 32 patients randomized into 2 groups applied either clobetasol foam 0.05% to the skin and scalp or combination clobetasol cream 0.05% to the skin and clobetasol solution 0.05% to the scalp. Psoriasis severity was measured using the standardized Psoriasis Area and Severity Index (PASI) and self-administered PASI (SAPASI). QOL was assessed via the EuroQoL-5D (EQ-5D) questionnaire and Dermatology Life Quality Index (DLQI). Cost-effectiveness was measured by the amount of medication used per body surface area (BSA) treated and by cost per point improvement in PASI score. In this study, a foam formulation performed better than a cream/solution combination by several measures. A greater absolute improvement in psoriasis severity was seen in the group using the foam than in the group using the cream/solution (mean decrease in PASI=5.0 vs 3.3, P=.05). The PASI score in the foam group decreased by 41% versus 35% in the cream/solution group (P=.17). In scalp psoriasis, the group using the foam had greater improvement in both absolute (P=.03) and percentage (P=.03) terms and than the solution group. When measuring global QOL, foam users had a significantly greater increase in EQ-5D than those using the cream/solution in absolute (P=.05, P=.02) and percentage (P=.04, P=.02) terms (first and second survey components, respectively). Differences in improvement of skin-specific QOL, quantified by DLQI scores between groups, were suggested but not statistically significant. Patients using foam spent less time applying medication compared with previous topical medications (P<.001). No significant difference in cost was appreciated between foam and cream/solution over the period after controlling for BSA (8.18 dollars vs 7.05 dollars per percentage BSA affected, P=.30).     

Efficacy and tolerability of topical 1% cidofovir cream for the treatment of external anogenital warts in HIV-infected persons

BACKGROUND: Treatment options for anogenital warts in patients with HIV-1 are unsatisfactory because they fail to eradicate latent human papillomavirus. GOAL: To determine tolerability and efficacy of topical 1% cidofovir cream for the treatment of external anogenital warts in HIV-infected patients. STUDY DESIGN: A randomized, placebo-controlled, single-blind, crossover pilot study of either 1% cidofovir cream or placebo applied once daily 5 days a week for 2 weeks followed by 2 weeks of observation was performed. RESULTS: Six patients were randomized to 1% cidofovir cream and six to placebo. The latter patients eventually received 1% cidofovir cream. Thus, 12 treatment rounds of cidofovir were compared with six rounds of placebo. A reduction of more than 50% in the total wart area achieved by seven cidofovir treatments (58%), as compared with no placebo regimen (P = 0.02). Local reactions occurred in 10 of the 12 patients treated with cidofovir, as compared with 0 of the 6 subjects in the placebo group (P < 0.001). CONCLUSIONS: For the initial clearance of anogenital warts in HIV-infected patients, 1% cidofovir cream is significantly more effective than vehicle cream. Local mucosal erosion is a common side effect.     

Treatment of rosacea with 1% metronidazole cream. A double-blind study

Eighty-one patients with rosacea were treated with either I% metronidazole cream or the cream base as a placebo for two months. The trial was performed double-blind, and the patients were assessed once each month. The variates studied were: (I) overall clinical assessment, (2) lesion counts, (3) degree of erythema, (4) independent photographic evaluation, and (5) patient's opinion. Four patients dropped out of the trial (one treated with metronidazole, three with placebo). In all the variates, I% metronidazole cream proved to be significantly more effective than placebo.     

0.1%他扎罗汀乳膏短时接触治疗寻常痤疮的疗效观察

［目的］对比观察及评价0.1%他扎罗汀乳膏短时接触治疗与常规每日一次治疗轻中度寻常型痤疮的疗效和安全性。［方法］采用前瞻性开放性对照观察,选用重庆华邦公司0.1%他扎罗汀乳膏局部外用面部轻中度痤疮,短时接触疗法为每晚1次,5分钟后洗去,常规疗法为每晚1次过夜,疗程均为8周,于第1、2、4、8周进行复诊随访。短时接触治疗组为52例,常规治疗组为49例。［结果］第8周时0.1%他扎罗汀短时接触治疗组有效率为69.1%,常规治疗组有效率为75.1%,X2=6.501,P=0.09＞0.05,两组疗效之间无显著统计学差异。不良反应发生率短时接触治疗组为21.2%,常规治疗组为44.9%,X2=8.538,P=0.036＜0.05,两组不良反应发生率有显著统计学差异,短时接触治疗组明显低于常规治疗组。［结论］他扎罗汀短时接触治疗寻常型痤疮安全、有效,值得临床推广应用。     

Efficacy of anti-sebum moisturizing cream containing 2% l-carnitine and 5% epigallocatechin gallate in seborrhea: A randomized clinical trial

Background

Seborrhea leads to facial greasiness and unpleasant feeling. People with seborrhea also have trouble with selecting moisturizers. l -Carnitine and epigallocatechin gallate (EGCG) are reported anti-sebum properties. However, neither efficacy comparison nor the combination effect of the two topical anti-sebum agents was studied. Moisturizing cream with these agents is supposed to provide skin with an optimal water–oil balance.

Aims

To compare the efficacy of moisturizer containing 2% l -carnitine or 5% EGCG alone on sebum controlling, and the synergistic effect of these two agents.

Methods

Three study creams were formulated by adding three kinds of anti-sebum agents which were 2% l -carnitine, 5% EGCG, and 2% l -carnitine plus 5% EGCG in moisturizing cream base of dimethicone and glycerin. A randomized clinical trial was conducted. Ninety subjects, divided into three groups, applied the cream for 4 weeks. Sebum level, skin capacitance, and transepidermal water loss (TEWL) were evaluated at Weeks 0, 1, 2, and 4. Life qualities and subjective outcomes were assessed before and after treatment.

Results

The mean sebum reduction from baseline was statistically significant in all treatment groups (p < 0.01). The median time to oil control was longer in l -carnitine group. The combine group had significantly greater anti-sebum efficacy than l -carnitine group (p = 0.009). All three groups had significant improvement of other objective parameters and subjective outcomes.

Conclusions

The anti-sebum moisturizing cream exhibited beneficial effect on the sebum reduction with improve skin hydration in people with seborrhea and made users satisfied. The EGCG group and the combine group show the greater anti-sebum effect than the l -carnitine group.     

Randomized placebo-controlled trial of metronidazole 1% cream with sunscreen SPF 15 in treatment of rosacea

Background: Rosacea is a photoaggravated dermatosis responsive to treatment with topical and oral antibiotics. A formulation combining metronidazole 1% cream with sunscreen SPF 15 was developed for the treatment of rosacea. Objective: The objective of this study was to determine the safety and efficacy of a formulation combining metronidazole 1% cream with sunscreen SPF 15 in the treatment of moderate to severe rosacea. Methods: One hundred and twenty patients with moderate to severe rosacea were enrolled for a randomized, placebo-controlled (vehicle containing sunscreen with SPF 15), double-blind study. Study cream was applied twice daily to the entire face over a 12-week period. Results: Treatment with metronidazole 1% cream with sunscreen SPF 15 resulted in significant improvement (p <0.05) in inflammatory lesion count, erythema and telangiectasiae scores, and investigator and patient global assessment scores compared with baseline and placebo. Adverse reactions related to study medication were typically mild, occurred at the site of application, and were reversible. There was no difference between the safety profiles of metronidazole 1% cream with sunscreen SPF 15 and placebo. Conclusions: The combined topical formulation of metronidazole 1% cream with sunscreen SPF 15 was an effective, well-tolerated topical agent for the treatment of moderate to severe rosacea.     

Safety and tolerability of combination acyclovir 5% and hydrocortisone 1% cream in adolescents with recurrent herpes simplex labialis

A Phase 3, open-label, multicenter study was conducted to assess the safety of the combination of 5% acyclovir and 1% hydrocortisone cream (AHC cream) in the treatment of recurrent herpes simplex labialis (HSL) in immunocompetent adolescents. Eligible subjects were aged 12 to 17 years and had a history of recurrent labial herpes with two or more episodes during the last 12 months. Subjects initiated treatment at the first signs or symptoms of a herpes recurrence-at the earliest prodromal phase and preferably before the presence of papules or vesicles. Subjects applied the cream topically five times per day for 5 days. Adverse events, categorization of recurrence (ulcerative or nonulcerative), and maximum lesion area (maximum area of an ulcerative lesion) were assessed. Of the 134 subjects analyzed for safety, 131 had data for categorization of recurrence at the post-treatment visit 3 ± 1 weeks after the last dose. Seventy-eight subjects (59.5%) had nonulcerative recurrences, and 53 (40.5%) had ulcerative recurrences. All 131 subjects reached the stage of normal skin, with no signs or symptoms, at the follow-up visit. The mean maximum lesion area in the 53 subjects with ulcerative herpes lesion was 39 mm(2). Five subjects reported five adverse events (secondary herpes labialis recurrences, n = 2; infectious rhinitis, n = 1; application site inflammation, n = 1; bronchial asthma, n = 1). All adverse events were of mild to moderate intensity. The results of this study demonstrate that the combination of AHC cream is well tolerated in the treatment of recurrent HSL in adolescents.     

Cumulative irritation potential of adapalene 0.1% cream and gel compared with tretinoin microsphere 0.04% and 0.1%

Despite the many beneficial effects of dermatologic applications, most of the current treatments for acne cause local irritation. The objective of this study was to compare the ability of the epidermis to tolerate adapalene 0.1% cream and gel and tretinoin microsphere in concentrations of 0.04% and 0.1%. A total of 31 subjects were enrolled in the study. The test products were applied under occlusive dressings on the upper back for approximately 24 hours, 4 times a week, and for 72 hours, once a week, for a period of 3 weeks. Skin reactions (erythema score plus other local reactions) at the product application sites were assessed 5 to 30 minutes after dressing removal. Twenty-six subjects completed the study. A total of 10 subjects discontinued use of 1 or more of the test products because of irritation scores reaching severe or greater, all of these discontinuations were at sites treated with the tretinoin products. The mean 21-day cumulative irritancy indices for adapalene 0. 1% cream and gel were significantly lower (P<.01) than those for tretirnoin microsphere 0.04% and 0. 1% and not higher than that of the negative control product.     

A comparison of triple combination cream and hydroquinone 4% cream for the treatment of moderate to severe facial melasma

The aim of this study was to compare the efficacy and safety of a triple combination (TC) cream and monotherapy with hydroquinone (HQ) cream in the treatment of moderate to severe facial melasma. A total of 120 patients applied TC cream once daily or HQ cream twice daily for 8 weeks. Evaluations included static global severity assessment of melasma, improvement of melasma over time, local tolerability, and adverse events. TC cream was significantly more effective than HQ cream from week 4 onwards: lesions were approximately equivalent to the surrounding skin in 35% of all TC-treated patients, compared to 5% of those who used HQ cream (P = 0.0001). Improvement of more than 75% was achieved by 73% of TC cream patients and 49% of HQ cream patients (P = 0.007). The incidence of adverse events (erythema, burning sensation, and desquamation) was similar in both groups. No patient dropped out of the study because of drug-related adverse events. TC cream was more effective than the HQ cream for the treatment of moderate to severe facial melasma. Both products had similar safety profiles.