Translate this page into:
Safety evaluation of pirfenidone gel 8% w/w: Assessing comedogenicity, skin irritability, allergenicity, and photoirritation
-
Received: ,
Accepted: ,
How to cite this article: Marathe V, Poojary P, Chitre T, Panda M, Mohanasundaram S, Sawant S, et al. Safety evaluation of pirfenidone gel 8% w/w: Assessing comedogenicity, skin irritability, allergenicity, and photoirritation. CosmoDerma. 2026;6:25. doi: 10.25259/CSDM_243_2025
Abstract
Objectives:
Hypertrophic scars are a pathological outcome of disrupted wound healing. These scars significantly affect the quality of life due to their esthetic, functional, and psychological impacts. Topical pirfenidone, a broad-spectrum antifibrotic agent, has shown potential in regulating collagen synthesis and reducing established scars. This study aimed to assess the safety profile of pirfenidone gel 8% w/w through standardized evaluations of its comedogenic potential, skin irritation on normal and sensitive skin, allergenicity, and photoirritation potential.
Materials and Methods:
The study employed a monocentric, evaluator-blinded design to assess the safety of pirfenidone in 281 participants. Comedogenicity was evaluated using follicular biopsy and microscopic grading. Skin irritation was measured with a patch test on sensitive and normal skin types, and outcomes were graded using the Draize and Contact Dermatitis Research Group scales. Allergenicity was assessed through a Human Repeat Insult Patch Test, while photoirritation was evaluated using a photo patch test.
Results:
Pirfenidone gel 8% w/w was noncomedogenic, with a mean comedone grade significantly lower than the positive control (P = 0.005). The patch test confirmed the gel’s non-irritant nature, with mean scores considerably lower than the positive control across sensitive and normal skin types. Allergenicity testing in 211 participants confirmed the gel as non-irritant and hypoallergenic, with no weak or strong positive reactions observed. Photoirritation testing classified the gel as a non-photo irritant, with mean scores for ultraviolet-exposed and ultraviolet-unexposed sites below the irritation threshold.
Conclusion:
This study demonstrates that pirfenidone gel 8% w/w is safe for topical application, with no significant adverse reactions observed concerning comedogenicity, skin irritability, allergenicity, and photoirritation. These findings support its use, although further research is warranted to evaluate its long-term safety.
Keywords
Allergenicity
Hypertrophic
Pirfenidone
Scars
Wound healing
INTRODUCTION
The wound-healing process is a complex physiological response comprising four overlapping phases: hemostasis, inflammation, proliferation, and remodeling.[1-3] These stages involve intricate molecular interactions between profibrotic and antifibrotic factors, including growth factors, proteolytic enzymes, and extracellular matrix (ECM) components.[4] During the proliferation phase, growth factors such as transforming growth factor-beta (TGF-β) and vascular endothelial growth factor drive angiogenesis, fibroblast proliferation, and ECM deposition, which is regulated by matrix metalloproteinases.[5] The subsequent remodeling phase restores tissue integrity through a balance of ECM synthesis and degradation. Disruptions in this balance, marked by excessive deposition of collagen, fibronectin, and proteoglycans, along with inadequate ECM remodeling, can result in hypertrophic scar formation.[4,6] Central to this pathology is dysregulation in TGF-β signaling, which enhances collagen production and inhibits its breakdown, contributing to excessive ECM accumulation.[7]
Hypertrophic scars are raised, erythematous lesions confined to the wound boundary, often resulting in esthetic concerns, functional limitations, discomfort, and psychological distress.[1,8,9] Their development is influenced by multiple intrinsic and extrinsic factors, including age, genetics, hormonal status, immune function, wound depth, anatomical location, and mechanical tension.[1] Triggers include surgical incisions, burns, trauma, tattoos, vaccinations, and inflammatory dermatoses such as acne or chickenpox.[6,10] Endothelial dysfunction and prolonged inflammation are hypothesized mechanisms that contribute to fibroblast dysregulation and fibrotic scarring.[11]
Certain demographic groups are more susceptible to hypertrophic scarring, particularly individuals aged 11–30 years, those with darker skin tones, and wounds located in high-tension areas such as the chest and shoulders.[12] Globally, the burden of hypertrophic scarring is substantial, especially in burn survivors. Annually, millions are affected, with studies reporting hypertrophic scar formation in 40–70% of surgical wounds and 32–72% of burn injuries.[13,14]
Managing hypertrophic scars remains challenging, largely due to the underlying excessive fibrosis. Pirfenidone, a broad-spectrum antifibrotic agent, has demonstrated efficacy in modulating fibroblast activity and downregulating cytokines such as TGF-β1.[6,15] In vitro and in vivo studies indicate that pirfenidone reduces the production of collagen and fibrotic markers such as alpha-smooth muscle actin, and its topical formulation has shown promise in mitigating established scars.[15]
However, topical therapies require stringent safety assessments to ensure tolerability, especially for long-term or repeated use. Potential risks include comedogenicity, irritation, allergenicity, and photoirritation.[16] While preclinical studies support the antifibrotic action of pirfenidone, clinical evaluation of its safety profile on diverse skin types is essential.
This study aims to assess the dermatological safety of pirfenidone gel 8% w/w using validated methods to evaluate comedogenic potential, skin irritation, allergenicity, and photoirritation. The findings will help determine its suitability for use on Indian skin and support its broader application in the management of hypertrophic scars.
MATERIALS AND METHODS
Study overview
The study objectives, design, and evaluation criteria are outlined in Table 1. The study protocol underwent review and received approval from the Independent Ethics Committee (Re-Registration number: ECR/245/Indt/MH/2015/RR-22). The test product evaluated was Pirfesca (PIRFENIDONE GEL 8% w/w) - B. No: 824-578, manufactured by Cipla Ltd., India. The study was conducted using the principles outlined in the Declaration of Helsinki, Good Clinical Practice guidelines, and the Indian Council of Medical Research guidelines concerning human medical research. In addition, the study method was based on the Bureau of Indian Standards (BIS) IS 4011:2018 guidelines, “Methods of Test for Safety Evaluation of Cosmetics - Third Revision.”[17] Before screening, the investigator thoroughly explained the study’s purpose, potential risks, and benefits to the participants. Informed consent was then obtained from all participants.
| Assessment | Study objective | Study design | Evaluation criteria |
|---|---|---|---|
| Comedogenicity | To evaluate the comedogenic potential of the test product when applied topically under an occluded patch to the skin, compared to controls | Evaluator-blinded, monocentric, comparative versus control | Grading of micro-comedones using light microscopy |
| Patch test | To evaluate the skin safety of the test product using 24-h patch tests under occlusion on adult, healthy human participants (50% with sensitive skin and 50% with normal skin) | Monocentric, nonrandomized, single-blinded, single-application, controlled study | Evaluation of cutaneous tolerance by dermatological scoring of skin reactions (erythema, edema, dryness, scaling, wrinkling) using the Draize scale |
| Allergenicity | To evaluate the skin irritation and sensitization potential (allergenicity) of the test product using the HRIPT technique in men and women | Monocentric, nonrandomized, evaluator-blinded trial where results were compared with an initial state and a negative control | Scoring of induction phase reactions using the Draize scale; scoring of challenge phase reactions as per the ICDRG scale |
| Photoirritation | To evaluate the potential of the test product to induce photoirritation in adult participants, using a photo patch test (single exposure to UV-A) | Monocentric, nonrandomized, single application, blinded, controlled study where results were compared with the initial state and the control site | Evaluation of skin irritation reactions (erythema, edema, dryness, scaling, wrinkling) using the Draize scale |
HRIPT: Human repeat insult patch test, ICDRG: International contact dermatitis research group, UV-A: Ultraviolet A
Sample size
Sample sizes for each safety assessment were determined based on the guidance outlined in BIS IS 4011:2018 or previously published peer-reviewed studies evaluating cosmetic and topical product safety, rather than formal power calculations, as the study was designed to assess tolerability and safety endpoints. For the comedogenicity assessment, 18 participants were selected.[18] The suggested sample sizes for the patch test, allergenicity test, and photoirritation test in BIS IS 4011:2018 are 24, 200, and 24, respectively.[17] This study included 26 participants for the patch test, 211 participants for the allergenicity test, and 26 participants for the photoirritation test.
Inclusion/Exclusion criteria
Eligible participants were healthy males and females aged 18– 65 years with skin phototypes III–V and no dermatological pathology on the test area. They were required to adhere to study procedures, avoid intense ultraviolet (UV) exposure and activities involving water contact or sweating, and demonstrate the ability to understand study instructions in English, Hindi, or a local language. Valid proof of identity and age, along with signed informed consent, was mandatory.
Exclusion criteria included pregnancy or lactation; presence of scars, tattoos, terminal hair, or skin infections at the test site; hypersensitivity to cosmetics or related products; significant systemic or chronic illnesses; or ongoing treatments that could interfere with the study. Individuals participating in another clinical or cosmetic study or within a defined exclusion period were also ineligible.
Comedogenicity test
For comedogenicity assessment, three 3 × 3 cm2 sites were marked on the upper back of each participant using a template for the positive control (coconut oil), negative control (glycerin), and test product (pirfenidone gel 8% w/w). A baseline follicular biopsy was performed at each site using 1–2 drops of cyanoacrylate adhesive on a glass slide, pressed onto the skin for 30–60 s, then gently removed to obtain the specimen.
About 2 h later, 0.025 g of each product was applied using 2 × 2 cm2 patch chambers. Clinical research assistants applied the patches under investigator supervision. Patches were initially applied 2 h post-biopsy and removed after 24 h. Patches were then reapplied on the same site every 48 h, with interim checks every 24–48 h for adverse events. This cycle was followed till patches were applied 12 consecutive times on alternate days (excluding Sundays). The application cycle was carried out weekly from Monday to Friday. On the final study day, a post-application follicular biopsy was performed 2 h after patch removal to assess comedogenicity. Microcomedones were graded under light microscopy on a 0–3 scale: 0 = None; 1 = Small microcomedones; 2 = Moderate, widespread microcomedones; and 3 = Large, globoid microcomedones covering the field.
Patch test
The patch test included a preliminary lactic acid sting test to identify participants with sensitive skin. In this test, 10% w/w aqueous lactic acid was randomly applied with a cotton pad to the nasolabial fold and cheek area on one side of the face, while water was applied to the opposite side. The lactic acid solution and water were unlabeled, ensuring that neither the investigator nor the participants knew which solution was applied to each side. Participants rated any irritation on a 4-point (0 = None, 1 = Mild, 2 = Moderate, and 3 = Severe) scale at 2.5, 5, and, if needed, 8 min after application.[19] Participants with a cumulative score of ≥3 across two or more time points were considered positive on the lactic acid sting test (i.e., having sensitive skin) and were included in the study.
Approximately 0.04 g of pirfenidone gel 8% w/w was filled in patch chambers and applied to the participants’ backs as an occlusive dressing. In addition, filter papers soaked in 0.9% isotonic saline (negative control) and 1% w/w sodium lauryl sulfate solution (positive control) were placed in separate patch chambers and applied to test sites, followed by occlusion. Patches were secured using a micropore tape. The patches were left in place for 24 h.
During Visit 2 (24 h after application), the patches were removed. During Visit 3 (48 h after application), the test areas were examined to assess skin reactions and scored using the Draize scale.[17,20] The Draize scale is a scoring system used to determine skin irritancy by evaluating reactions such as erythema (redness/dryness/wrinkles) and edema (swelling) on a scale of 0–4, with higher scores indicating more severe reactions. For erythema/dryness/wrinkles, scores range from 0 (no redness) to 4 (severe redness), while for edema, scores range from 0 (no swelling) to 4 (severe swelling). The analysis was based on the combined mean score obtained 24 h after the patch removal. The mean score for irritation was calculated as the total score (erythema + edema) for each sample divided by the total number of subjects. A mean score up to 2.0/8.0 was classified as non-irritant, a score of >2.0/8.0 to 4.0/8.0 was classified as mildly irritant, and a score of >4.0/8.0 was classified as irritant. Participants who showed reactions at the 48-h mark were called for a follow-up visit in 1 week (Visit 4) to confirm recovery from irritation.
Allergenicity test
A patch test was conducted by applying approximately 0.04 g of 8% w/w pirfenidone gel to designated chambers on participants’ backs. Control chambers contained filter papers soaked in 0.09% isotonic saline. The study consisted of two phases: the induction phase and the challenge phase. During the induction phase, patches were applied on alternate days at Visits 1, 3, 5, 8, 10, 12, 15, 17, and 19 and removed on the following visits (Visits 2, 4, 6, 9, 11, 13, 16, 18, and 20). Skin reactions were scored at each assessment visit starting from Visit 3, using the Draize scale, which evaluates erythema/dryness/wrinkles and edema on a 0–4 scale, with higher scores indicating more severe reactions.
Following a 14-day rest period, the challenge phase commenced. Patches were applied to new sites adjacent to the original induction sites at Visit 22 and removed after 24 h (Visit 23). Scoring of skin reactions was conducted at 48 h (Visit 24), 72 h (Visit 25), and 96 h (Visit 26) using the International Contact Dermatitis Research Group (ICDRG) scale, a scoring system specific for allergic contact dermatitis in response to patch testing.[17,21] The ICDRG scale categorizes responses as negative (no reaction), doubtful (erythema only, no infiltration), weak positive (+; erythema, infiltration, possibly discrete papules), strong positive (++; erythema, infiltration, papules, vesicles), and extreme positive (+++; erythema, infiltration, confluent vesicles). An irritant reaction (different types of reactions, such as soap effect, vesicles, blisters, necrosis) category was also included to identify non-allergic irritation. Participants showing reactions were followed up after 1 week to ensure that any reactions had subsided.
Photoirritation test
In the photoirritation test, two duplicate test sites (2 × 2 cm2) were marked on each participant’s back, and 0.04 g of the test product was applied to each site using patch chambers. Sites were occluded. After 24 h, one of the patches was removed, and the underlying skin was exposed to UV-A (5 J/cm2). The site was covered again. The other duplicate patch was left undisturbed to serve as a control for comparison. In addition, a separate adjacent site was exposed to UV light as a control for UV exposure. After another 24 h, all the patches were removed. The study followed a structured visit schedule. Visit 1 included explaining the study procedure, obtaining informed consent, conducting inclusion/exclusion screening, and applying the initial patches. At Visit 2 (24 h), one patch was removed, UV exposure was applied to the test site, the patch was reapplied, and adverse events were checked. Visit 3 (48 h) involved the removal of all patches, scoring test areas for skin reactions using the Draize scale (with erythema, dryness, wrinkles, and edema assessed on a 0–4 scale), and assessing any adverse events. Visit 4 (1 week) provided a follow-up for participants with reactions, confirming recovery and resolution of any irritation. The Draize scale was used to score the combined mean reaction of erythema, dryness, wrinkles, and edema for both exposed and unexposed sites.
RESULTS
The mean age and number of participants for each safety evaluation are outlined in Table 2.
| Test | Age in years (mean±SD) | N | Males | Females |
|---|---|---|---|---|
| Comedogenicity | 40.18±8.87 | 18 | 0 | 18 |
| Patch test | 29.58±10.88 | 26 | 13 | 13 |
| Allergenicity | 37.09±10.01 | 211 | 19 | 192 |
| Photoirritation | 34.58±11.40 | 26 | 13 | 13 |
N: Sample size, SD: Standard deviation
Comedogenicity
The comedogenicity assessment included 18 female participants with a mean age of 40.18 ± 8.87 years. The mean comedones grade observed was 1.06 ± 0.94 with the application of pirfenidone gel 8% w/w, 2.00 ± 0.69 with the positive control (coconut oil), and 0.56 ± 0.78 with the negative control (glycerin) [Figure 1]. The statistical comparison showed that the mean comedones grade was significantly (P = 0.001) lower for the negative control (glycerin) than the mean grade of the positive control (coconut oil). Furthermore, the mean comedones grade for pirfenidone 8% w/w gel was significantly (P = 0.005) lower than the mean grade of the positive control (coconut oil). This comparison between the positive and negative controls was conducted to validate the protocol, confirming that the study design could accurately differentiate comedogenic potential. The results indicate that pirfenidone gel 8% w/w is noncomedogenic. In addition, one participant reported lesions on the hand and back, accompanied by fever, and the patient was discontinued. Symptoms for the discontinued patient subsided on follow-up 1 week later.
- Mean comedone grades observed after the application of the test product and the control.
Patch test
The patch test was conducted on 26 participants, comprising 13 males and 13 females, with a mean age of 29.58 ± 10.88 years. The mean A + O score was 0.54 for participants with sensitive skin, 0.31 for those with normal skin, and the combined mean score for erythema, dryness, wrinkles, and edema (A + O) after applying pirfenidone gel 8% w/w was 0.42, as shown in Figure 2 and Table 3. Given that a combined mean score of up to 2.0 indicates a non-irritant product, these results confirmed that pirfenidone gel 8% w/w was non-irritant. No study-related adverse events or intolerances were observed throughout the study.
- Mean A + O scores from the patch test (combined, sensitive skin, and normal skin). A + O: Erythema, dryness, wrinkles, and edema.
| Group | Mean A+O score | Combined | |
|---|---|---|---|
| Sensitive skin | Normal skin | ||
| Pirfenidone gel | 0.54 | 0.31 | 0.42 |
| Negative control | 0 | 0 | 0 |
| Positive control | 3 | 2.93 | 2.96 |
A+O: Erythema, dryness, wrinkles, and edema
Allergenicity
The allergenicity assessment included 211 participants, 19 males and 192 females, with a mean age of 37.09 ± 10.01 years. During the induction phase, the mean cumulative score (A + O) for pirfenidone gel 8% w/w remained below 2 (0.65), classifying it as a non-irritant. In the challenge phase, participant responses to the gel were assessed at 48, 72, and 96 h. The number of participants without reactions increased over time, from 150 at 48 h to 168 at 72 h and 208 at 96 h, while doubtful reactions decreased progressively from 61 at 48 h to just 3 at 96 h [Table 4]. No weak positive, strong positive, extreme positive, or irritant reactions were observed with the test product at any time. The Human Repeat Insult Patch Test (HRIPT) findings confirmed that pirfenidone gel 8% w/w was non-irritant and hypoallergenic. In addition, no adverse events were reported during the study.
| Outcome | 48 h | 72 h | 96 h |
|---|---|---|---|
| Negative reaction | |||
| Control | 204 | 209 | 210 |
| Pirfenidone gel | 150 | 168 | 208 |
| Doubtful reaction | |||
| Control | 7 | 2 | 1 |
| Pirfenidone gel | 61 | 43 | 3 |
| Weak positive | |||
| Control | 0 | 0 | 0 |
| Pirfenidone gel | 0 | 0 | 0 |
| Strong positive | |||
| Control | 0 | 0 | 0 |
| Pirfenidone gel | 0 | 0 | 0 |
| Extreme positive | |||
| Control | 0 | 0 | 0 |
| Pirfenidone gel | 0 | 0 | 0 |
| Irritant | |||
| Control | 0 | 0 | 0 |
| Pirfenidone gel | 0 | 0 | 0 |
Photoirritation
The photoirritation test was conducted on 26 participants, consisting of 13 males and 13 females, with a mean age of 34.58 ± 11.40 years. This test assessed the skin reactions of A + O in response to pirfenidone gel 8% w/w. The combined mean score (A + O) for the unexposed site treated with the gel was 0.50, while the UV-exposed site scored 0.42 [Figure 3]. As both scores were below the threshold of 2, the test product was classified as non-photo–irritant, indicating minimal to no irritation with UV exposure. In addition, no study-related adverse events or intolerances were reported during the study.
- Combined mean A + O scores from the photoirritation test. A + O: Erythema, dryness, wrinkles, and edema.
DISCUSSION
Hypertrophic scars are a pathological consequence of chronic inflammation during wound healing, characterized by excessive fibrosis and disordered layers of skin proteins. Pirfenidone has been previously investigated for its role in modulating fibrosis and abnormal collagen deposition in scar-related conditions.[15,22] While its efficacy in scar reduction has been studied, the primary objective of this study was to evaluate its dermatological safety, including comedogenicity, irritability, allergenicity, and photoirritation.
Given its proposed topical application, the safety of pirfenidone gel must be thoroughly evaluated due to risks from topical chemical exposure.[16] This study is the first to evaluate the safety of 8% pirfenidone gel across comedogenicity, allergenicity, photoirritation, and skin irritation endpoints in an Indian population.
Results confirmed that pirfenidone gel is noncomedogenic, with significantly lower comedone grades than the positive control (coconut oil), indicating suitability for acne-prone users. Patch tests demonstrated non-irritant behavior across sensitive and normal skin. Combined scores for erythema, dryness, wrinkles, and edema were below irritation thresholds, with no adverse events. Allergenicity testing via HRIPT in 211 participants showed the gel is hypoallergenic, with no strong or weak positive reactions. Likewise, photoirritation testing showed no irritation in UV-exposed or unexposed sites, classifying the gel as nonphoto–irritant. Although photosensitivity is known with oral pirfenidone, it was not observed with the topical gel in this study.[23] This aligns with earlier reports where thrice-daily topical use for 6 months resulted in only minor, self-limiting effects such as pruritus and rash, which resolved in 1 month.[6] In addition to the findings of this study’s safety evaluation, supportive evidence from clinical studies further informs the overall safety profile of topical pirfenidone. Published clinical studies evaluating topical pirfenidone 8% gel in fibrotic dermatological conditions, including hypertrophic scars, diabetic foot ulcers, and localized scleroderma, have consistently reported a favorable safety profile.[24,25] In studies involving hypertrophic scars and localized scleroderma, pirfenidone 8% gel was administered three times daily for up to 6 months. Across these studies, no serious treatment-related adverse events and no clinically meaningful laboratory abnormalities were observed.[6,26] These findings further support the safety of pirfenidone when administered topically.
Although systemic administration represents a different route with distinct pharmacokinetic characteristics, the extensive clinical and post-marketing experience with oral pirfenidone provides additional reassurance regarding its overall safety profile. Oral pirfenidone has been approved for the treatment of idiopathic pulmonary fibrosis (IPF) and has been commercially available in India since 2010 and in the United States since 2014. A pooled analysis of four clinical trials in patients with IPF demonstrated that pirfenidone was safe and generally well tolerated when used systemically for up to 7.7 years.[27] While systemic exposure is not expected from topical use, these data further mitigates concerns regarding systemic pharmacokinetic risks.
Notably, pirfenidone’s safety profile extends to topical application on wounds, with no evidence of excessive healing delays.[22,28] However, while other interventions for hypertrophic scars, such as laser therapy, silicone sheets, and onion extract gel, are effective, they carry varying risks of adverse effects.[1,29-31] Pirfenidone gel offers a noninvasive alternative with minimal risks, further supporting its utility in clinical practice.
This study was limited to short-term application; future studies should evaluate long-term safety.
CONCLUSION
This study in Indian participants provides evidence supporting the safety of pirfenidone gel 8% w/w for topical use, addressing key concerns such as comedogenicity, allergenicity, and potential skin irritation under various conditions. The safety testing underscored its suitability for individuals seeking scar treatment without adverse skin reactions. These results established a foundation for the safe use of pirfenidone gel and positioned it as a promising option for managing hypertrophic scars. Continued research into long-term application and cumulative effects will further enhance the understanding of its safety and broaden its therapeutic potential in scar treatment.
Ethical approval:
The research/study was approved by the Institutional Review Board at Claims Independent Ethics Committee, number ECR/245/Indt/MH/2015/RR-22, dated February 03, 2024.
Declaration of patient consent:
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patients have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published, and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Conflicts of interest:
All the authors are employees of Cipla Ltd., Mumbai, Maharashtra, India.
Use of artificial intelligence (AI)-assisted technology for manuscript preparation:
The authors confirm that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript and no images were manipulated using AI.
Financial support and sponsorship: This study was funded by Cipla Ltd., Mumbai, Maharashtra, India.
References
- Current therapeutic approach to hypertrophic scars. Front Med (Lausanne). 2017;4:83.
- [CrossRef] [PubMed] [Google Scholar]
- Wound healing In: StatPearls. Treasure Island, FL: StatPearls Publishing; 2024. Available from: https://www.ncbi.nlm.nih.gov/books/NBK535406/?report=printable [Last accessed on 2025 Jul 07]
- [Google Scholar]
- Ferrer-Bruker. Hypertrophic scarring In: StatPearls. Treasure Island, FL: StatPearls Publishing; 2024. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470176/?report=printable [Last accessed on 2025 Jul 07]
- [Google Scholar]
- The molecular mechanism of hypertrophic scar. J Cell Commun Signal. 2013;7:239-52.
- [CrossRef] [PubMed] [Google Scholar]
- Transition from inflammation to proliferation: A critical step during wound healing. Cell Mol Life Sci. 2016;73:3861-85.
- [CrossRef] [PubMed] [Google Scholar]
- A controlled clinical trial with pirfenidone in the treatment of pathological skin scarring caused by burns in pediatric patients. Ann Plast Surg. 2012;68:22-8.
- [CrossRef] [PubMed] [Google Scholar]
- Current potential therapeutic strategies targeting the TGF-β/Smad signaling pathway to attenuate keloid and hypertrophic scar formation. Biomed Pharmacother. 2020;129:110287.
- [CrossRef] [PubMed] [Google Scholar]
- The roles of inflammation in keloid and hypertrophic scars. Front Immunol. 2020;11:603187.
- [CrossRef] [PubMed] [Google Scholar]
- Quality of life of patients with keloid and hypertrophic scarring. Arch Dermatol Res. 2006;297:433-8.
- [CrossRef] [PubMed] [Google Scholar]
- Hypertrophic scars and keloids: Etiology and management. Am J Clin Dermatol. 2003;4:235-43.
- [CrossRef] [PubMed] [Google Scholar]
- Endothelial dysfunction may play a key role in keloid and hypertrophic scar pathogenesis-keloids and hypertrophic scars may be vascular disorders. Med Hypotheses. 2016;96:51-60.
- [CrossRef] [PubMed] [Google Scholar]
- Scar epidemiology and consequences In: Textbook on scar Management: State of the Art Management and Emerging Technologies. Vol 8. Cham: Springer; 2020. p. :45-9.
- [CrossRef] [PubMed] [Google Scholar]
- Update on hypertrophic scar treatment. Clinics (Sao Paulo). 2014;69:565-73.
- [CrossRef] [Google Scholar]
- A scoping review of the methodology used in studies of genetic influences on the development of keloid or hypertrophic scarring in adults and children after acute wounding. Adv Wound Care (New Rochelle). 2021;10:557-70.
- [CrossRef] [PubMed] [Google Scholar]
- Pirfenidone attenuates the profibrotic contractile phenotype of differentiated human dermal myofibroblasts. Biochem Biophys Res Commun. 2020;521:646-51.
- [CrossRef] [PubMed] [Google Scholar]
- Review on safety assessment of a cosmetic product. Int J Curr Pharm Res. 2018;10:1-6.
- [CrossRef] [Google Scholar]
- IS 4011: Methods of Test for Safety Evaluation of Cosmetics. 2018 Available from: https://archive.org/details/gov.in.is.4011.2018 [Last accessed on 2025 Jul 07]
- [Google Scholar]
- Safety assessment on comedogenicity of dermatological products containing d-alpha tocopheryl acetate in Asian subjects: A double-blind randomized controlled trial. Contemp Clin Trials Commun. 2021;23:100834.
- [CrossRef] [PubMed] [Google Scholar]
- Questionnaire and lactic acid sting test play different role on the assessment of sensitive skin: A cross-sectional study. Clin Cosmet Investig Dermatol. 2021;14:1215-25.
- [CrossRef] [PubMed] [Google Scholar]
- Methods for the study of irritation and toxicity of substances applied topically to the skin and mucous membranes. J Pharmacol Exp Ther. 1944;82:377-90.
- [CrossRef] [Google Scholar]
- New antifibroblastic medication in dermatology: Could nintedanib treat scarring? Int J Gen Med. 2022;15:7169-72.
- [CrossRef] [PubMed] [Google Scholar]
- Severe photosensitivity reaction after pirfenidone use. Cureus. 2021;13:e16626.
- [CrossRef] [Google Scholar]
- Topical administration of pirfenidone increases healing of chronic diabetic foot ulcers: A randomized crossover study. J Diabetes Res. 2016;2016:7340641.
- [CrossRef] [PubMed] [Google Scholar]
- Pirfenidone in skin fibrosis and scarring: From bench insights to clinical data. Med Sci (Basel). 2025;13:148.
- [CrossRef] [PubMed] [Google Scholar]
- Pirfenidone gel in patients with localized scleroderma: A phase II study. Arthritis Res Ther. 2015;16:510.
- [CrossRef] [PubMed] [Google Scholar]
- Comprehensive assessment of the long-term safety of pirfenidone in patients with idiopathic pulmonary fibrosis. Respirology. 2014;19:740-7.
- [CrossRef] [PubMed] [Google Scholar]
- Pirfenidone increases the epithelialization rate of skin graft donor sites. Burns. 2018;44:2051-58.
- [CrossRef] [PubMed] [Google Scholar]
- Hypertrophic scarring and keloids: Pathomechanisms and current and emerging treatment strategies. Mol Med. 2011;17:113-25.
- [CrossRef] [PubMed] [Google Scholar]
- Standard guidelines of care: Keloids and hypertrophic scars. Indian J Dermatol Venereol Leprol. 2011;77:94-100.
- [CrossRef] [PubMed] [Google Scholar]
- A new proprietary onion extract gel improves the appearance of new scars: A randomized, controlled, blinded-investigator study. J Clin Aesthet Dermatol. 2012;5:18-24.
- [Google Scholar]