Tretinoin, Adapalene, Tazarotene: Understanding the Difference Between Common Retinoids
Tretinoin,
Adapalene, Tazarotene: Understanding the Difference Between Common Retinoids
By
Sarah Taylor, PharmD
What
are retinoids?
Retinoids are
vitamin A (retinol) derivatives either synthetic or natural. Natural retinoid
derivatives include retinoic acid (tretinoin), and retinyl esters. Synthetic
retinoid derivatives include newer retinoids like tazarotene or adapalene. Retinoids
play a role in a wide variety of processes within the body including reproduction,
vision, inflammation, and cell differentiation and proliferation among others.1
Common retinoids such as tretinoin and adapalene are FDA approved for the
management of acne vulgaris, tazarotene is approved for use for acne as well as
plaque psoriasis.2,3,4 Currently, retinoids are approved for a
relatively limited number of conditions, but studies have been evaluating their
use for other purposes for many years. Some of these conditions include
management of scars/keloids or stretch marks, aging skin, hyperpigmentation,
rosacea, alopecia, and oral lichen planus. In this blog post, we’ll talk about
information to support the use of various retinoids for off label indications
and available information on comparative efficacy and tolerability.
Scars
and Stretch Marks
Fibroblasts play
an important role in wound healing, but scarring can develop as a result of
fibroblast activation resulting in excessive extracellular matrix deposition.5
Application of retinoids has been shown to decrease fibroblast proliferation
and studies of topical tretinoin 0.05% have found that application results in
marked scar size reduction and even a decrease in pruritis associated with
scarring.6 One study of both adapalene 0.3% and tazarotene 0.1% for
management of acne found significant improvement in macular acne scars in the tazarotene group.7,8 Another
study on adapalene compared to placebo did note that adapalene 0.3% gel
improved the appearance of skin texture and atrophic scars by 50% and 80%
respectively.9 In addition to general scaring and acne scars, some
studies have noted the benefit of retinoids for striae distensea (stretch
marks) as well. One study of tretinoin 0.1% noted reduction of length and width
of stretch marks over the 6-month study period.10
Photoaging
The proposed
mechanism of action for retinoids in aging skin is multifaceted, but in summary
it is thought that topical retinoids improve photoaging by increasing epidermal
proliferation, compacting the stratum corneum, preventing collagen degradation,
and by increasing synthesis of glycosaminoglycans by binding to certain areas
of DNA known as retinoic acid response elements.11 Tretinoin is
commonly used in concentrations ranging from 0.05 to 0.1% for this condition.
Placebo controlled trials lasting 3 to 12 months evaluating tretinoin 0.05%
have demonstrated tretinoin to be superior to placebo. Another
placebo-controlled, double-blind study of tretinoin 0.1% over a period of 16
weeks found significantly improved signs of photoaging in almost all patients
treated.12,13 Another randomized vehicle controlled parallel comparison
trial of tazarotene cream at various strengths compared to tretinoin 0.05%
cream and found tazarotene at higher concentrations (0.1%) was associated with
improved mottled hyperpigmentation and fine wrinkles compared to the tretinoin
0.05% group.14 Another double-blind randomized study comparing
tazarotene 0.1% to tretinoin 0.05% over a 24 week period also found tazarotene
to be more efficacious than tretinoin for fine and coarse wrinkling, overall
photodamage, and mottled hyperpigmentation. The study did note increased
irritation associated with tazarotene in the first week as compared to
tretinoin, but this difference was not noted beyond the first week.15
Hyperpigmentation
Retinoids such as
tretinoin suppress UVB induced pigmentation and promote increased epidermal
turnover to limit contact time between keratinocytes and melanocytes. Tretinoin
is also sometimes used in combination with hydroquinone to enhance penetration.
Skin lightening benefits may take longer to become apparent as comparted with
hydroquinone if used as a single agent.6 Tretinoin used in
combination with other agents, usually between 0.01-0.05%, or used as a single
agent, up to 0.1%, has been shown in placebo-controlled studies to decrease
pigmentation.16,17 Adapalene 0.1% has also been studied for
hyperpigmentation. One study of adapalene 0.1% gel in black patients found a
significant reduction in acne-associated hyperpigmentation.18
Another randomized double-blind placebo-controlled trial of tazarotene 0.1% for
post inflammatory hyperpigmentation in patients with darker skin found
significant improvement in area and intensity of hyperpigmentation over the
course of the 18-week study.19
Alopecia
In addition to
their many cosmetic indications, some retinoids have been studied for potential
benefit for alopecia. Tretinoin is thought to enhance minoxidil response in
patients with androgenetic alopecia. One study positing that tretinoin enhances
percutaneous delivery of minoxidil, compared minoxidil 5% applied twice daily
versus minoxidil 5% combined with 0.01% tretinoin applied once daily found that
once daily combination therapy was as effective as twice daily application of
minoxidil alone for patients with androgenetic alopecia.20,21
Information on the use of other retinoids, including adapalene and tazarotene,
for alopecia is limited. One study evaluating mometasone furoate 0.1% vs
mometasone furoate 0.1% in conjunction with adapalene 0.1% for alopecia areata
found statistically significant more hair growth with the combination product
than with mometasone alone over the 12-week study.22 At this time
studies evaluating tazarotene for alopecia are not available.
Acne
Tretinoin,
adapalene, and tazarotene are all FDA approved for acne. The mechanism of
action of retinoids for acne involves their effect on reducing keratinocyte
proliferation as well as their ability to block inflammatory pathways commonly
associated with the development of acne. Though retinoids share a mechanism of
action, studies have compared and contrasted them for acne and found
differences between them. Tazarotene 0.1% has been noted to be more effective
than tretinoin 0.025% or 0.1%, whereas adapalene 0.1% has been found to be equally
effective to tretinoin 0.025-0.1%, but significantly better tolerated than
tazarotene 0.1% gel and tretinoin 0.025-0.1% topical preparations.24
Another review of topical retinoids for acne found that patients on tretinoin 0.05%
had a higher incidence of adverse effects than adapalene at 0.1 and 0.3%
strengths.25 Studies have also suggested adapalene to be better
tolerated topically than tazarotene when both used at the same 0.1% strength.26
Psoriasis
Currently,
between adapalene, tretinoin, and tazarotene, only tazarotene is FDA approved
for psoriasis.4 One study evaluating the safety and efficacy of
tazarotene 0.1% compared to clobetasol propionate for palmoplantar psoriasis
found a similar success rate with both treatments with onset of efficacy being
faster for clobetasol up to 8 weeks, but at 12 weeks, both treatments were
equally efficacious.26 Other studies looking at combination therapy
noted that combination tazarotene 0.1% and mometasone 0.1% cream was better
tolerated and more efficacious than mometasone monotherapy for patients with
moderate to severe plaque psoriasis. The study posited that there may be a
benefit to the use of combination therapy to induce remission and then ongoing
treatment with tazarotene alone.27 Tazarotene has even been used at
0.05-0.1% topically to manage psoriasis of the nail.28,29
Stability
Tretinoin is
known to be prone to oxidation. One study evaluating tretinoin compatibility
with benzoyl peroxide noted significant degradation in just two hours when the
combination was exposed to light, whereas when protected from light degradation
didn’t occur over a 7-hour test period.30 Tretinoin alone, even
without benzoyl peroxide, can degrade 60-80% when exposed to normal daylight
over a period of 24 hours. Another study that looked at adapalene and tretinoin
under similar conditions combined with 10% benzoyl peroxide found significant
degradation of the tretinoin product, but noted good stability of adapalene
with benzoyl peroxide even in the presence of light over the 72 hour exposure
period.31 This increased stability is in part attributable to
structural changes in which the double bonds of the tretinoin molecule are
replaced by a more robust naphthoic acid aromatic ring.32 Though
still prone to photodegradation, tazarotene has also been noted to have superior
photostability to tretinoin with adapalene being considered the least prone to
photodegradation of the three.33,34 FDA approved topical tretinoin
products tend to contain stabilizers and antioxidants such as butylated
hydroxytoluene and/or butylated hydroxyanisole for stability as do tazarotene
preparations, whereas aqueous adapalene products do not.
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