Meta Information
ID:tretinoin
Name:Tretinoin
Schema Version:2.4_uniform_evidence_2026_06_18
Created
2026-05-21T22:30:00Z
Model
phase-a-upgrade-claude-sonnet-4.6
Interactions
Target id:
/condition/pregnancy
Target name:
Pregnancy
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Retinoids are known teratogens, meaning they can cause severe birth defects. Although systemic absorption from topical application is minimal, its use is strictly contraindicated during pregnancy due to the high risk to the fetus.
Actionable advice:
This should be strictly avoided during pregnancy, when planning to become pregnant, or if pregnancy is possible.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
holoprosencephaly
Label source:
FDA label: Tretinoin (Retin-A Micro)
Action type:
avoid
Target id:
/lifestyle/sun-exposure
Target name:
Sun Exposure (UV Radiation)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Tretinoin increases the skin's sensitivity to ultraviolet (UV) light by thinning the stratum corneum, significantly raising the risk of sunburn, cellular damage, and photoaging.
Actionable advice:
Minimize direct sun exposure and use broad-spectrum sunscreen daily.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
Avoid unprotected exposure to sunlight including sunlamps
Label source:
FDA label: Tretinoin (Retin-A Micro)
Action type:
informational_none
Target id:
/intervention/sunscreen
Target name:
Broad-Spectrum Sunscreen (SPF)
Severity:
major
Interaction type:
requirement
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Daily use of broad-spectrum sunscreen is essential to protect photosensitized skin from UV damage, preventing sunburn and mitigating the risk of photoaging.
Actionable advice:
A broad-spectrum sunscreen with SPF 30 or higher should be applied every morning without fail.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
Use sunscreen of at least SPF 15 and protective clothing
Label source:
FDA label: Tretinoin (Retin-A Micro)
Action type:
informational_none
Target id:
/circadian/sleep
Target name:
Bedtime / Night
Severity:
major
Interaction type:
requirement
Nature:
temporal
Temporal spacing:
Hours before target:
0.5
Hours after target:
null
Description:
Tretinoin is chemically unstable and degrades upon exposure to UV light, which significantly reduces its efficacy. Applying it at night in the dark ensures maximum therapeutic activity.
Actionable advice:
Tretinoin should be applied once daily in the evening, ideally 30 minutes before bed.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
topical application in the treatment of acne vulgaris
Label source:
FDA label: Tretinoin (Retin-A Micro)
Action type:
informational_none
Target id:
/procedure/skin-resurfacing-procedures
Target name:
Skin Resurfacing Procedures (Lasers, Peels, Microneedling)
Severity:
major
Interaction type:
adverse
Nature:
temporal
Temporal spacing:
Hours before target:
168
Hours after target:
168
Description:
Procedures like chemical peels, laser treatments, or microneedling disrupt the skin barrier. Using tretinoin too close to these procedures can impair healing, cause excessive irritation, and lead to adverse outcomes like hyperpigmentation.
Actionable advice:
Tretinoin should be discontinued for 5-7 days before and after procedures like chemical peels or laser treatments.
Validation status:
validated_via_expert_review
Evidence tier:
tier_c
Evidence basis:
expert_review_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Retin-A Micro should not be used on eczematous or sunburned skin
Label source:
FDA label: Tretinoin (Retin-A Micro)
Action type:
avoid
Target id:
/procedure/facial-waxing
Target name:
Facial Waxing
Severity:
major
Interaction type:
adverse
Nature:
temporal
Temporal spacing:
Hours before target:
120
Hours after target:
48
Description:
Tretinoin thins the stratum corneum, making the skin more fragile. Waxing can lift or tear this delicate skin, a phenomenon known as 'skin lifting', causing significant injury and potential scarring.
Actionable advice:
Tretinoin should be stopped on the area for at least 5 days before waxing, with a 2-day wait afterward.
Validation status:
validated_via_expert_review
Evidence tier:
tier_c
Evidence basis:
expert_review_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Retin-A Micro should not be used on eczematous or sunburned skin
Label source:
FDA label: Tretinoin (Retin-A Micro)
Action type:
avoid
Target id:
/condition/compromised-skin-barrier
Target name:
Compromised Skin Barrier (Eczema, Rosacea)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Applying tretinoin to skin with a compromised barrier, such as in eczema or active rosacea, can cause severe irritation, inflammation, and worsen the underlying condition.
Actionable advice:
This should not be applied to areas with active eczema, rosacea, sunburn, or broken skin.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
Retin-A Micro should not be used on eczematous or sunburned skin due to
Label source:
FDA label: Tretinoin (Retin-A Micro)
Action type:
informational_none
Target id:
/class/ahas-bhas
Target name:
Exfoliating Acids (AHAs/BHAs) (Ahas Bhas)
Severity:
moderate
Interaction type:
adverse
Nature:
temporal
Temporal spacing:
Hours before target:
12
Hours after target:
12
Description:
Both tretinoin and exfoliating acids (e.g., glycolic, salicylic acid) increase skin cell turnover and can be irritating. Using them together can lead to over-exfoliation, excessive dryness, redness, and a damaged skin barrier.
Actionable advice:
These are best used on alternate nights, or the exfoliating acid in the morning and tretinoin at night.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
acne preparations containing benzoyl peroxide, sulfur, resorcinol, or salicylic acid with Retin-A Micro
Label source:
FDA label: Tretinoin (Retin-A Micro)
Action type:
informational_none
Target id:
/intervention/benzoyl-peroxide
Target name:
Benzoyl Peroxide
Severity:
moderate
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
8
Hours after target:
8
Description:
Benzoyl peroxide is an oxidizing agent that can chemically degrade the tretinoin molecule, rendering it less effective if they are applied at the same time.
Actionable advice:
Applications should be separated by at least 8 hours, typically using benzoyl peroxide in the morning and tretinoin at night.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
acne preparations containing benzoyl peroxide, sulfur, resorcinol, or salicylic acid with Retin-A Micro
Label source:
FDA label: Tretinoin (Retin-A Micro)
Action type:
separate
Target id:
/intervention/vitamin-c-topical
Target name:
Topical Vitamin C (L-Ascorbic Acid)
Severity:
moderate
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
8
Hours after target:
8
Description:
Vitamin C (L-ascorbic acid) is formulated at a low pH for stability and penetration, which can destabilize tretinoin (which prefers a more neutral pH) and increase the potential for skin irritation when applied together.
Actionable advice:
Vitamin C is best applied in the morning and tretinoin at night to ensure efficacy and tolerability of both.
Validation status:
unvalidatable
Evidence tier:
tier_e
Evidence basis:
unvalidatable
Evidence anchors:
Source url:
Scientific literature support not found
Exact phrase from label:
Label source:
FDA label: Tretinoin (Retin-A Micro)
Action type:
informational_none
Target id:
/class/photosensitizing-agents
Target name:
Photosensitizing Medications
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Concomitant use of systemic or topical photosensitizing drugs (e.g., tetracyclines, thiazides, quinolones, St. John's Wort) can have an additive effect, further increasing the risk of severe phototoxic reactions or sunburn.
Actionable advice:
Exercise extreme caution with sun protection if taking other photosensitizing medications.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
heightened susceptibility to sunlight as a result of the use of tretinoin
Label source:
FDA label: Tretinoin (Retin-A Micro)
Action type:
informational_none
Target id:
/condition/lactation
Target name:
Breastfeeding (Lactation)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
It is not known whether topical tretinoin is excreted in human milk. Due to the theoretical potential for risk to the nursing infant, its use is generally not recommended while breastfeeding.
Actionable advice:
Tretinoin is best avoided while breastfeeding unless specifically cleared by a physician.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
Nursing Mothers
Label source:
FDA label: Tretinoin (Retin-A Micro)
Action type:
avoid
Target id:
/class/abrasive-scrubs
Target name:
Abrasive or Medicated Cleansers and Scrubs (Abrasive Scrubs)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Abrasive scrubs, harsh soaps, and medicated cleansers can compromise the skin barrier, leading to increased sensitivity, redness, and irritation when used with tretinoin.
Actionable advice:
A gentle, hydrating, non-medicated cleanser is best used alongside tretinoin.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
acne preparations containing benzoyl peroxide, sulfur, resorcinol, or salicylic acid with Retin-A Micro
Label source:
FDA label: Tretinoin (Retin-A Micro)
Action type:
informational_none
Target id:
/class/denatured-alcohol-toners
Target name:
Alcohol-Based Toners and Astringents (Denatured Alcohol Toners)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Products containing high concentrations of denatured alcohol, such as some toners and astringents, are excessively drying and will exacerbate the irritation and peeling caused by tretinoin.
Actionable advice:
Alcohol-based toners or astringents are best avoided in a skincare routine.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
acne preparations containing benzoyl peroxide, sulfur, resorcinol, or salicylic acid with Retin-A Micro
Label source:
FDA label: Tretinoin (Retin-A Micro)
Action type:
avoid
Target id:
/class/sulfur-acne-products
Target name:
Sulfur-Based Topical Products (Sulfur Acne Products)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Topical products containing sulfur, often used for acne, can have a significant drying effect on the skin, which is compounded by the drying nature of tretinoin, leading to excessive irritation.
Actionable advice:
Sulfur-containing acne treatments or soaps are best avoided in the same routine as tretinoin.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
acne preparations containing benzoyl peroxide, sulfur, resorcinol, or salicylic acid with Retin-A Micro
Label source:
FDA label: Tretinoin (Retin-A Micro)
Action type:
avoid
Target id:
/intervention/ceramides
Target name:
Ceramides
Severity:
moderate
Interaction type:
synergistic
Nature:
temporal
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Moisturizers containing ceramides help to repair the skin's natural barrier, reduce transepidermal water loss, and mitigate the irritation, dryness, and peeling commonly caused by tretinoin.
Actionable advice:
A ceramide-rich moisturizer is best applied nightly, either before or after tretinoin, to improve tolerance.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Ceramide-containing moisturizers reduce tretinoin-induced irritation
Label source:
Primary literature: https://pubmed.ncbi.nlm.nih.gov/17129262/
Action type:
informational_none
Target id:
/intervention/topical-niacinamide
Target name:
Niacinamide (Topical)
Severity:
minor
Interaction type:
synergistic
Nature:
temporal
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Niacinamide can help improve skin barrier function, increase ceramide production, and has anti-inflammatory properties that may decrease the irritation and redness associated with retinization.
Actionable advice:
Consider incorporating a niacinamide serum into your routine, applying it before tretinoin.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Topical niacinamide combined with retinoids improves tolerability
Label source:
Primary literature: https://pubmed.ncbi.nlm.nih.gov/30746931/
Action type:
informational_none
Target id:
/intervention/hyaluronic-acid
Target name:
Hyaluronic Acid
Severity:
minor
Interaction type:
synergistic
Nature:
temporal
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Hyaluronic acid is a humectant that draws moisture into the skin, helping to counteract the dryness and flaking that can be caused by tretinoin, thereby improving skin hydration and comfort.
Actionable advice:
A hyaluronic acid serum may be applied to damp skin before other products to boost hydration.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Hyaluronic acid moisturizers improve retinoid tolerance
Label source:
Primary literature: https://pubmed.ncbi.nlm.nih.gov/17129262/
Action type:
informational_none
Target id:
/class/exfoliating-acids
Target name:
Sulfur-Based Topical Products
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
Description:
Topical products containing sulfur, often used for acne, can have a significant drying effect on the skin, which is compounded by the drying nature of tretinoin, leading to excessive irritation.
Actionable advice:
Sulfur-containing acne treatments or soaps are best avoided in the same routine as tretinoin.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Established mechanism / class pharmacology (no single primary source quoted)
Exact phrase from label:
Dermatologic inference: combining drying topicals (e.g., sulfur-containing acne products, AHAs/BHAs) with tretinoin compounds dryness/irritation and barrier disruption; introduce gradually and moisturize. Practical.
Label source:
Class inference
Action type:
avoid
Derived From
tretinoin_local_healthspan
Provenance Note
Interactions duplicated from 'tretinoin_local_healthspan'. Topical tretinoin; same local interactions.