Expert Opinion on Investigational Drugs

ISSN: 1354-3784 (Print) 1744-7658 (Online) Journal homepage: http://www.tandfonline.com/loi/ieid20

Bimatoprost for the treatment of eyelash, eyebrow

and scalp alopecia

Yevher Lorena Barrn-Hernndez & Antonella Tosti

To cite this article: Yevher Lorena Barrn-Hernndez & Antonella Tosti (2017) Bimatoprost for the
treatment of eyelash, eyebrow and scalp alopecia, Expert Opinion on Investigational Drugs, 26:4,
515-522, DOI: 10.1080/13543784.2017.1303480

To link to this article: http://dx.doi.org/10.1080/13543784.2017.1303480

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Mar 2017.
Published online: 16 Mar 2017.

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EXPERT OPINION ON INVESTIGATIONAL DRUGS, 2017
VOL. 26, NO. 4, 515522
http://dx.doi.org/10.1080/13543784.2017.1303480

DRUG EVALUATION

Bimatoprost for the treatment of eyelash, eyebrow and scalp alopecia

Yevher Lorena Barrn-Hernndeza and Antonella Tostib
a
Department of Dermatology, General Hospital Dr. Manuel Gea Gonzlez, Mexico City, Mexico; bDepartment of Dermatology and Cutaneous
Surgery, University of Miami, Miller School of Medicine, Miami, FL, USA

ABSTRACT ARTICLE HISTORY

Introduction: Alopecia is a common condition observed among people of all ages. It is a disorder that Received 29 September 2016
can involve only the scalp as observed in androgenetic alopecia or scalp and body as in alopecia areata Accepted 3 March 2017
or patients under chemotherapy treatment. There are several treatment options with different safety KEYWORDS
and efficacy outcomes. Bimatoprost, a synthetic prostamide F2 analog originally approved for the Androgenetic alopecia;
treatment of ocular hypertension and open-angle glaucoma, is now FDA approved as a 0.03%, solution alopecia areata; bimatoprost;
to be applied once daily to increase eyelashes growth. chemotherapy-induced
Areas covered: In this review, the authors evaluate the role of bimatoprost in idiopathic hypotrichosis alopecia; eyebrows;
of the eyelashes, in hypotrichosis of the eyelashes associated to chemotherapy, in alopecia areata of the eyelashes; hypotrichosis;
eyelashes and eyebrows and in androgenetic alopecia. In addition, pharmacokinetics, pharmacody- prostamide
namics, safety and tolerability of bimatoprost are discussed.
Expert opinion: Bimatoprost will likely be the third FDA approved weapon in the fight against hair loss.
Prostaglandin analogs are the only possible treatment for hypotrichosis and alopecia of the eyelashes
regardless of its etiology. Eyebrow hypotrichosis due to alopecia areata or frontal fibrosis alopecia can
also possibly benefit of these medications.

1. Introduction inhibitors such as ruxolitinib and tofacitinib are a new promis-

Alopecia is a common condition observed among general popu-
lation. Androgenetic alopecia (AGA) is the most common cause
of hair loss. It is a multifactorial and polygenic disorder charac-
terized by a progressive thinning of scalp hair in a distinctive
pattern [1]. It affects both genders with a male predominance [2].
It could be present at puberty with an increased frequency with
age [3]. The prevalence differs between races. It is observed in up
to 80% of Caucasian men [4] with a lower prevalence in African
[5] and Asian population [2]. The therapeutic recommendation
for males with AGA consists in topical minoxidil 5% solution/
foam twice daily or oral finasteride 1 mg a day, the combination
of these medications could be use for greater efficacy. Another
option to be considered is oral dutasteride 0.5 mg a day [68].
The treatment recommended for females with AGA is topical
minoxidil 2% solution 1 ml twice daily, or 5% foam once a day.
Oral antiandrogens and 5 alpha reductase inhibitors can be
considered in female AGA patients even though data on efficacy
are not very strong [68].
Another type of hair loss is alopecia areata (AA), an auto-
immune disorder characterized by a non-scarring alopecia of
the scalp and body. It is the second most prevalent alopecia
after AGA with a lifetime incidence of approximately 2% in the
global population [9]. AA is difficult to treat and randomized
controlled trials are limited. In general, potent topical or intra-
lesional steroids are recommended for limited disease,
whereas systemic steroids, oral immunosuppressants, photo-
therapy, and contact immunotherapy are utilized for extensive
disease including alopecia totals/universalis [911]. JAK
ing therapeutic choice for AA. Recent studies show that these
drugs induce hair regrowth in patients with moderate-to-
severe AA [12,13].
Chemotherapy induced alopecia (CIA) is a distressing side
effect that greatly affects quality of life of patients, the inci-
dence is approximately 65% [14]. There are no available phar-
macological interventions to decrease the risk of CIA. The
scalp protection through hypothermia minimizes delivery of
chemotherapeutic agents to the scalp and its effectiveness in
preventing hair loss depends on chemotherapy type and dose
[15]. Topical minoxidil does not prevent hair loss but may be
helpful to accelerate regrow [16].
2. Body of review
2.1. Overview of the market
Only few topical agents have been shown to promote hair
grow in controlled studies. Minoxidil is an effective topical
product that is FDA-approved for treating male and female
AGA [6,7]. Furthermore, it is also commonly utilized as an off-
label medication in the treatment of AA [17,18]. Despite of its
significant clinical efficacy it is not effective in all patients and
requires long-term use to maintain results [19].
Cyclosporine A (CSA), an immunosuppressive agent, has
been shown to induce hair growth after systemic or topical
use [20]. Although topical CSA has been occasionally utilized
in the treatment of AA [21] and AGA [22], the lack of clinical
trials has limited its use to exceptional cases.

CONTACT Yevher Lorena Barrn-Hernndez lorenabarronh@hotmail.com

2017 Informa UK Limited, trading as Taylor & Francis Group
516 Y. L. BARRN-HERNNDEZ AND T. ANTONELLA
Box 1. Drug summary box.
Drug name (generic): Bimatoprost
Phase:III
Indication: hypotrichosis of the eyelashes
Pharmacology description/mechanism of action: synthetic prostamide
F2 analog
Route of administration: topical
Chemical structure: see attached
Pivotal trial (s): NCT00693420 [45,46]
Latanoprost, bimatoprost, and travoprost are analogs of pros-
taglandin (PG) used to treat glaucoma that have been shown to
stimulate eyelash growth [23,24]. Pilot studies show that latano-
prost is effective in the treatment of AGA [25] and hypotrichosis
of the eyelashes caused by AA [26].
Options to enhance the appearance of eyelashes include
cosmetics and camouflage products. Mascara is an available
and not expensive option, but the effects are temporary and
cannot be utilized when the eyelashes are absent as in AA or
chemotherapy alopecia [27].
Many over-the-counter cosmetic products advertised as
eyelash grow promoters that contain PG analogs [28] or cop-
per peptides [29] are available, but neither the safety nor
efficacy of these products has been completely studied.
Human hair eyelashes or synthetic eyelashes are another
option but cannot be used on a daily basis and the glues
required for the application can cause contact dermatitis and
damage natural eyelashes [30].
Hair transplant is not only effective in the treatment of AGA
of the scalp [31], but has been successfully utilized in hypo-
trichosis of the eyelashes [32,33], eyebrows, beard, and side-
burns [33].
2.2. Introduction to the compound
Bimatoprost is a synthetic prostamide F2 analog, which mimics
the hypotensive ocular action of the endogenous prostamide
[34]. It is used for the treatment of ocular hypertension, open-
angle glaucoma [35] and for the treatment of hypotrichosis of
the eyelashes [36]. For the reduction of elevated intraocular
pressure, bimatoprost is available as 0.1 mg/mL and 0.3 mg/
mL solution that is administered at the dose of one drop in the
affected eye(s) once a day in the evening [35]. For the treatment
of hypotrichosis of the eyelashes, bimatoprost is available as
0.3 mg/mL solution that is nightly directly at the base of the
eyelashes through a special applicator [36].
2.3. Chemistry
The chemical name of Bimatoprost is (Z)-7-[(1 R,2 R,3 R,5S)-3,5-
Dihydroxy-2-[(1E,3S)-3-hydroxy-5-phenyl-1-pentenyl] cyclopen-
tyl]-5-N-ethylheptenamide and the molecular formula is
C25H37NO4 (Box 1). It is a white to off-white powder with a
molecular mass of 415.58. It is very soluble in alcohols, very
slightly soluble in water and practically insoluble in toluene and
hexane. LUMIGAN 0.01% and 0.03% is an isotonic (approxi-
mately 290 mOsmol/kg) and colorless ophthalmic solution [35].
The composition of bimatoprost ophthalmic solution is:
bimatoprost (0.1 mg/mL or 0.3 mg/mL), benzalkonium chlor-
ide (antimicrobial preservative), sodium phosphate dibasic
heptahydrate and citric acid (buffering agents), sodium chlor-
ide (tonicity adjuster) and sodium hydroxide and hydrochloric
acid (pH adjusters) and purified water. The pH during its shelf
life ranges from 6.8 to 7.833. The composition of bimatoprost
0.03% ophthalmic solution (bimatoprost 0.3 mg/mL) pre-
scribed for reduction of elevated intraocular pressure is iden-
tical to the bimatoprost 0.03% solution approved for
hypotrichosis of the eyelashes [36].
2.4. Pharmacodynamics
PG ethanolamides (prostamides) are members of the fatty acid
amide family [37]. Bimatoprost is the first member of the prosta-
mide drug class; it is a synthetic molecule structurally and phar-
macologically similar to PG F2 1-ethanolamide (prostamide
F2) [38]. The biosynthetic pathway for prostamide F2 starts
with the conversion of phosphatidylethanolamine (membrane
phospholipid) by phospholipase D into anandamide, ananda-
mide is then converted into a prostamide H2 by cyclo-oxyge-
nase-2 (oxygenation) and finally this endoperoxide intermediate
is converted into prostamide F2 by an aldo-keto reductase
family 1 member C3 (AKR1C3) also known as PGF synthetase
[34,39]. This enzyme has a broad distribution and its physiologic
significance is uncertain. Recently another enzyme, prostamide/
PGF synthetase has been identified, it is a member of thioredoxin
superfamily and it converts prostamide H2 into prostamide F2.
It can be found in the brain and spinal cord [39].
Bimatoprost is not considered a prodrug because it does
not require to be converted to an active metabolite to exert its
pharmacological activity. The affinity of bimatoprost to a vari-
ety of receptors has been studied and it has been shown that
its effects do not depend of interaction with adrenergic, cho-
linergic, cannabinoid, dopaminergic, or prostanoid receptors
[34]. Bimatoprost specifically binds to the prostamide receptor
that is pharmacologically distinct from the prostanoid FP
receptors, which are the target for PG analogs [39].
Murine models have been used to study the mechanism of
eyelashes growth induced by PGF2 alpha analogs, as the general
morphology of mouse eyelids is compatible with human eyelids.
It has been observed that bimatoprost has a hair growth-stimu-
latory effect and increases the eyelash length without generation
of new follicles. Bimatoprost also affects the eyelash growth cycle

by increasing the percentage of anagen follicles. It promotes
anagen reentry of telogen eyelash follicles and prolongs the
anagen phase by arresting catagen entry. Finally, it also increases
eyelash thickness by increasing hair bulb diameter [40].
2.5. Pharmacokinetics and metabolism
After administration of one drop of bimatoprost ophthalmic solu-
tion, maximum plasma concentration is reached within 10 min
and the lowest concentration is observed after 1.5 h [41]. Most of
the drug remains in the plasma and it is moderately distributed
into body tissues with a steady state of 0.67 L per kg. The plasma
protein binding of bimatoprost is approximately 88% [35].
The elimination half-life is approximately 45 min, and urin-
ary excretion accounts for two-thirds of total elimination of
bimatoprost administrated intravenously, with the remainder
being excreted in feces. Systemic exposure to bimatoprost is
very low after ocular administration [35].
Bimatoprost ophthalmic solution applied directly at the
base of the eyelashes through an applicator delivers approxi-
mately 5% of the volume of the drop administered for the
treatment of glaucoma [42].
2.6. Clinical efficacy
2.6.1. Role of bimatoprost in hypotrichosis of the
eyelashes
Bimatoprost ophthalmic solution, 0.03% was approved by US
Food and Drug Administration (FDA) in December 2008 for
the treatment of hypotrichosis of the eyelashes. The drug was
developed for this indication after many studies reported
hypertrichosis of the eyelashes as a side effect of bimatoprost
in patients with glaucoma [42].
Eyelash hypotrichosis is a condition characterized by inade-
quate amount of eyelashes that can be caused by multiple
factors, including aging, heredity, physical trauma, eye surgery,
trichotillomania, AA, chemotherapy, and unknown causes [43]. It
is a condition that not only has a negative impact on self-image,
but also in increasing risk of ocular injury [44].
Efficacy of bimatoprost 0.03% solution has been evaluated in
clinical trials for the treatment of idiopathic [4547] or che-
motherapy-induced eyelash hypotrichosis [4749] and AA
[49,50]. Smith et al. performed a clinical trial to compare the
safety and efficacy of bimatoprost 0.03% (applied once a day to
upper eyelid margins) versus vehicle on eyelash length, thick-
ness, and darkness in subjects with idiopathic hypotrichosis.
The results of this trial showed that the 78.1% of patient treated
with bimatoprost had at least a one-grade increase in global
eyelash assessment score at week 16 in comparison with 18.4%
of subjects in the vehicle group (P < .0001). Subjects in the
bimatoprost 0.03% group also had significant increases in eye-
lash length, thickness, and darkness (P < .0001) [45].
In a randomized, double-blinded, vehicle-controlled, paral-
lel- group study among subjects with idiopathic hypotrichosis,
Fagien et al. evaluated patient-reported outcomes of bimato-
prost ophthalmic solution 0.03% for eyelash growth and found
that bimatoprost group reported significantly greater
EXPERT OPINION ON INVESTIGATIONAL DRUGS 517
improvements from baseline on all eyelash satisfaction ques-
tionnaire items at four months of treatment (P .0433) [46].
In a Japanese study, the effect of bimatoprost 0.03% versus
vehicle was assessed in 173 subjects with idiopathic hypotri-
chosis and found that the 77.3% of bimatoprost-treated sub-
jects had at least a one-grade improvement in global eyelash
assessment score from baseline to month 4 compared with
17.6% of vehicle-treated subjects (P < 0.001) [47].
The effect of bimatoprost solution 0.03% on eyelash
growth in patients with chemotherapy-induced eyelash
hypotrichosis was examined in a double-blinded, rando-
mized, and placebo-controlled study that showed that treat-
ment with bimatoprost recovered eyelash growth more
quickly than the natural course observed in the vehicle con-
trol group [48].
In a multicenter, double-blinded, randomized parallel-
group study of 36 patients with chemotherapy-induced eye-
lash hypotrichosis, the intervention group (n = 18) received
bimatoprost 0.03 % applied once daily to the upper eyelid
margins for 4 months, resulting in at least a one-grade
improvement in global eyelash assessment score in 88.9% of
patients vs. 27.8% in vehicle group, (P < 0.001) [47].
Borchet et al. performed a clinical trial in pediatric popula-
tion to evaluate the safety and efficacy of bimatoprost solu-
tion 0.03% for eyelash growth in healthy adolescents and
patients with hypotrichosis caused by chemotherapy or AA
and concluded that bimatoprost treatment was effective in
healthy adolescents but not in those with eyelash hypotricho-
sis due to chemotherapy or AA [49].
There is not enough evidence of efficacy of bimatoprost solu-
tion 0.03% for the treatment of hypotrichosis due to AA. A clinical
trial (NCT00187577) evaluating efficacy of latanoprost and bima-
toprost solution in promoting eyelash growth in patients with AA
has been completed, but there are no results available yet [50].
However, in a 1-year retrospective study of 41 patients with AA
universalis who applied 0.03% bimatoprost to the eyelid margin
once a day for 1 year, the authors reported total or moderate
growth of the eyelashes in 43.24% of the patients [51].
In order to allow a precise application of bimatoprost to the
upper eyelid, some studies have used a bimatoprost gel pre-
paration rather than the standard solution. Wester et al. con-
ducted a study in 19 females to evaluate eyelash growth from
application of bimatoprost in gel suspension to the base of the
eyelashes compared to application of hydroxypropyl methylcel-
lulose in gel suspension, and found a statistically significant
difference in the length of the lashes in the bimatoprost-treated
group compared to the placebo group (P = 0.009) [52]. Similar
findings were observed by Woodward et al. who conducted a
prospective, double-blinded, randomized controlled study in 52
patients without ocular disease and found that bimatoprost
0.03% gel once a day improved eyelash length compared to
control group (P = 0.004) [53].
The efficacy of bimatoprost eyelash gel to improve hypotri-
chosis caused by chemotherapy was evaluated in randomized,
single-blinded, prospective, internally controlled trial. In total,
40 eyelids of 20 chemotherapy-treated breast cancer patients
were randomized to treatment or control and it was observed
518 Y. L. BARRN-HERNNDEZ AND T. ANTONELLA
that there was a significant difference in eyelash length
(P = 0.02), pigment (P = 0.06), and thickness (P = 0.01) at
month 3 of evaluation between treated and controls [54].
Table 1 summarizes the results of the available trails for
bimatoprost in the treatment eyelash hypotrichosis.
2.6.2. Role of bimatoprost in hypotrichosis of the
eyebrows
Data on efficacy of bimatoprost in eyebrow hypotrichosis are
mostly anecdotal. However, Beer et al. reported significant
improvement of mild to moderate eyebrow hypotrichosis
after application of bimatoprost 0.03% ophthalmic solution
daily for 9 months in a randomized, double-blind, vehicle-
controlled pilot study [55] (Table 2).
The first large, phase III, randomized, vehicle-controlled
study to evaluate safety and efficacy of bimatoprost 0.03% in
subjects with eyebrow hypotrichosis has recently been pub-
lished by Carruthers et al. Authors randomized 357 subjects
with eyebrow hypotrichosis to receive bimatoprost 0.03%
twice or once daily or vehicle twice daily. After 7 months of
treatment, they observed a significantly higher proportion of
subjects with at least a onegrade increase in Global Eyebrow
Assessment in the bimatoprost groups compare with vehicle
(P < 0.001). No differences were observed between bimato-
prost groups [56] (Table 2).
2.6.3. Role of bimatoprost in AA of the scalp
Data on efficacy of bimatoprost on AA are conflicting. Most of
the studies with PG analogues are focused on treatment of the
AA of the eyelashes [49,50]. Zaher et al. were the first to
perform a study on patients with AA of the scalp. They
included 30 adults with patchy AA with 25% of hair loss
and compared the response to topical application of bimato-
prost 0.03% solution applied twice daily to one AA patch
versus mometasone furoate cream 0.1% applied once daily
to another non adjacent AA patch. After 3 months therapy,
the authors observed higher percentage of hair re-growth
(P = 0.001), earlier onset of initial response (P = 0.005) and
lower incidence of resistance (P = 0.02) and relapses (P = 0.03)
in the bimatoprost 0.03% group [57]. However, further studies
with longer follow-up and larger sample sizes are required.
2.6.4. Role of bimatoprost in AGA
Clinical trials evaluating safety and efficacy of bimatoprost in
men and women with AGA have been completed.
A phase II, randomized, double-blinded, crossover study
(NCT02170662) was designed to determine the effect of bimato-
prost solution on scalp hair growth. Nine men with AGA
(Hamilton-Norwood: IIIv, IV, V and Va) were included. The first
group (3 patients) applied placebo topically during 16 weeks and
then bimatoprost 0.03% solution during 16 weeks with a 10-day
washout period and the second group (6 patients) applied bima-
toprost 0.03% solution and then placebo during the same period.
The preliminary results showed that after the first part of treat-
ment (16 weeks), the percent change in Target Area Total Hair
Count was greater in the second group (27.4 vs. 2.6) [58].
Two more trials to evaluate safety and efficacy of bima-
toprost in men with mild to moderate AGA were designed.
The first study was a phase II, randomized double-blinded
study (NCT01325337) performed in 307 men to compare 3
formulations of bimatoprost solution (A, B, C) with vehicle
and minoxidil 5% solution. The dose and duration treatment
for each group was 1 ml once daily for 6 months except for
minoxidil 5% solution that was applied twice daily. The
preliminary results showed a greater change from baseline
in Target Area Hair Count (TAHC) in the minoxidil 5% group
compared to vehicle and bimatoprost groups (A: 13.1; B: 6.1;
C: 6.3; vehicle: 4.1 and minoxidil 5%: 21.9 terminal hairs/
cm2) [59]. The second study is a phase II, randomized dou-
ble-blinded study (NCT01904721) performed in 244 men to
compare two formulations of bimatoprost solution with
vehicle. The patients applied bimatoprost and vehicle
twice daily for 6 months. The preliminary results showed a
greater change in TAHC in bimatoprost groups compared to
vehicle (formulation 1: 12.7, formulation 2: 9.3 and vehicle
5.8 terminal hairs/cm2) [60].
A phase II, randomized, double-blinded study
(NCT01325350) evaluated safety and efficacy of bimato-
prost in 306 women with mild to moderate AGA. Three
formulations of bimatoprost solution (A, B, C) were com-
pared with vehicle and minoxidil 2% solution. The dose
and duration treatment for each group was 1 ml once daily
for 6 months except for minoxidil 2% solution that was
applied twice daily. The preliminary results showed a
greater change from baseline in TAHC in the minoxidil
2% group compare to vehicle and bimatoprost groups (A:
0.4; B: 3.5; C: 4.3; vehicle: 1.1 and minoxidil 2%: 13.6
terminal hairs/cm2) [61].
2.7. Safety and tolerability
Bimatoprost 0.03% applied once daily to increase eyelashes
growth has shown to be safe and well tolerated in adult and
pediatric populations, with few discontinuations due to
adverse events (AEs). In a pooled safety analysis of six rando-
mized, double-blinded clinical trials, most of the reported AEs
were mild, localized to the site of application and reversible
with interruption of the treatment. The most commonly
reported AEs were conjunctiva hyperemia (6.3%), eyelid prur-
itus (3.4%), eyelid pigmentation (3.4%), nasopharyngitis (3.4%),
erythema of the eyelid (3.2%), and punctate keratitis (3.2%).
The iris hyperpigmentation is believed to be an irreversible
side effect, however, in this polled safety analysis, just two
cases were reported. No significant changes in biomicroscopy,
ophthalmoscopy, intraocular pressure, or visual acuity were
observed [62].
Side effects reported in clinical trials of bimatoprost for treat-
ment of AGA include dryness (6.56%) [61], irritation (7.69%),
contact dermatitis (7.69%) [60], and pruritus (11.48%) [59,61].
2.8. Regulatory affairs
Based on the extensive safety database for bimatoprost for the
treatment of glaucoma (9 phase I and II studies and 2 pivotal
phase III studies), additional clinical study data, post marketing
surveillance data and 1 additional pivotal confirmatory study
Table 1. Clinical trials evaluating efficacy and safety of bimatoprost for the treatment of hypotrichosis of the eyelashes.
Trial Aim
Smith et al. 2012 [45] To compare the safety and efficacy of
bimatoprost 0.03% solution versus
vehicle in increasing eyelash length,
thickness, and darkness
Efficacy parameter:
investigator-assessed GEA score of
prominence
Fagien et al. 2012 [46] To asses patient-reported outcomes
after treatment with bimatoprost
0.03% applied once daily to upper
eyelid margins
Efficacy parameter: self- reported ESQ
Harii et al. 2014 [47] To evaluate the efficacy and safety of
bimatoprost 0.03% for Japanese
subjects
Efficacy parameter: investigator-assessed
GEA score of prominence
Ahluwalia 2013[48] To evaluate the safety and efficacy of
bimatoprost solution 0.03% in
increasing overall eyelash
prominence
Efficacy parameter: investigator-assessed
GEA score of prominence
Harii et al. 2014 [47] To evaluate the efficacy and safety of
bimatoprost 0.03% for Japanese
subjects
Efficacy parameter: investigator-assessed
GEA score of prominence
Borchet et al. 2016 [49] To evaluate safety and efficacy of
bimatoprost 0.03% solution for
treatment of eyelash hypotrichosis in
a pediatric population
Efficacy parameter: investigator-assessed
GEA score of prominence
Vila et al. 2010 [51] To evaluate bimatoprost 0.03% solution
for eyelash growth in patients with
AA
Efficacy parameter: investigator-assessed
eyelashes regrowth
Wester et al. 2010 [52] To determine if bimatoprost 0.03% gel
causes increased lash length
Efficacy parameter: investigator-assessed
eyelashes length
Woodward et al. 2010 [53] To evaluate a bimatoprost 0.03% gel in
enhancing eyelash growth, adverse
effects, and change in IOP
Efficacy parameter: investigator-assessed
eyelashes length
Morris et al. 2011 [54] To assess bimatoprost 0.03% gel in
increasing eyelash growth, amount,
pigment, and thickness
Efficacy parameter: investigator-assessed
eyelashes length, amount,
pigmentation and thickness
GEA: Global Eyelash Assessment; ESQ: Eyelash Satisfaction Questionnaire; AA: alopecia areata; IOP: intraocular pressure.
Study design
Phase III, multicenter, randomized, double
blinded, vehicle-controlled study Duration:
4-month treatment period and 1-month
post-treatment follow up
Phase III, multicenter, randomized, double
blinded, vehicle-controlled study Duration:
4-month treatment period and 1-month
post-treatment follow up
Phase III, multicenter, double blinded,
parallel-group, vehicle-controlled study
Duration: 4-month treatment period and 1-
month post-treatment follow up
Phase III, multicenter, double blinded,
randomized, parallel-group study.
Duration: 12-month treatment period
Phase III, multicenter, double blinded,
parallel-group, vehicle-controlled study
Duration: 4-month treatment period and 1-
month post-treatment follow up
Phase IV, multicenter, randomized, double
blinded, parallel-group study Duration:4-
month treatment period and 1-month
post-treatment follow up
Retrospective Duration: 1-year treatment
period
Prospective, randomized controlled double
blind study Duration: 6-week treatment
period and 3-month post-treatment
follow up
Prospective, doublemasked, randomized
controlled study
Duration: 6-month follow up period
Randomized, single-blinded, prospective,
internally controlled trial
Duration: 3-month follow up period
No. of subjects and characteristics Conclusions
278 adults with idiopathic hypotrichosis Bimatoprost Bimatoprost was effective at enhancing
0.03% solution: 37 Vehicle: 141 eyelashes with a good safety profile
278 adults with idiopathic hypotrichosis Bimatoprost Bimatoprost was effective at producing more
0.03% solution: 137 Vehicle: 141 prominent eyelashes
173 adults with idiopathic hypotrichosis Bimatoprost Bimatoprost was effective and safe in producing
0.03% solution:88 Vehicle: 85 longer, thicker, darker and more prominent
eyelashes
130 subjects with eyelash hypotrichosis due to Bimatoprost was effective and well tolerated
chemotherapy over the 1-year treatment period
Bimatoprost 0.03% solution:96 Vehicle:34
36 adults with chemotherapy-induced hypotrichosis Bimatoprost was effective and safe in producing
Bimatoprost 0.03% solution:18 Vehicle:18 longer, thicker, darker and more prominent
eyelashes
71 children with eyelash hypotrichosis Bimatoprost Bimatoprost treatment was effective in healthy
0.03%:48 (healthy subjects: 26, adolescents but not in those with eyelash
postchemotherapy:13, and AA:9) Vehicle: 23 hypotrichosis due to chemotherapy or AA
(healthy subjects:14, postchemotherapy:3, and
AA:6)
41 adults and children with eyelash hypotrichosis due Bimatoprost may be effective and safe in the
to AA treatment of eyelash hypotrichosis due to AA
19 adults applied bimatoprost gel to one eyelid and Bimatoprost gel increased eyelash length
control gel to the fellow eyelid
52 adult subjects without ocular disease Bimatoprost gel was effective in enhancing
Bimatoprost gel:36 Control gel:16 eyelash growth with conjunctival and eyelid
hyperemia as the most common adverse
effect and a reduction in mean IOP
20 female adults with chemotherapy-induced eyelash Bimatoprost gel seems promising for eyelash
hypotrichosis applied bimatoprost to one eyelid, hypotrichosis due to chemotherapy
EXPERT OPINION ON INVESTIGATIONAL DRUGS
leaving the fellow eyelid as control
519
520 Y. L. BARRN-HERNNDEZ AND T. ANTONELLA

to assess eyelash growth, a new drug application (NDA) for

Bimatoprost effective, well tolerated,

bimatoprost solution 0.03% for the treatment for hypotrichosis
of eyelashes was approved by FDA on December 2008 [42].

Bimatoprost was effective at

improving appearance of
Bimatoprost ophthalmic solution is approved worldwide for

Conclusions

and safe for eyebrow

the treatment of glaucoma.

hypotrichosis
3. Conclusion

eyebrows
In this review, we have exposed the most recent literature
available for bimatoprost for the treatment of alopecia. Clinical
results with bimatoprost 0.03% ophthalmic solution have
Bimatoprost BID: 118 Bimatoprost QD:118 Vehicle: 121 shown that this drug is effective and well tolerated and sys-
357 subjects with grade 1 or 2 eyebrow hypotrichosis

temically safe to the treatment of idiopathic eyelash hypotri-

chosis. Therapy with bimatoprost 0.03% could be a promising
No. of subjects and characteristics
20 subjects with mild to moderate eyebrow

alternative to chemotherapy-induced eyelash hypotrichosis,

AA-induced eyelash hypotrichosis, and idiopathic eyebrow
hypotrichosis. However, clinical studies, in particular phase III
trials, are needed to determine the efficacy, safety and dose of
bimatoprost to treat male and female AGA.

4. Expert opinion
hypotrichosis

New effective treatments for hair loss are a real medical need
as AGA and AA are very common and we currently don't have
much to offer to our patients. There are only two approved
treatments for AGA in men and one in women and we have
no approved treatments for AA. Most importantly, patients do
Phase III, randomized, double blinded,

and 1-month post-treatment follow

Randomized, double blinded, vehicle-

Duration: 9-month treatment period

Duration: 7-month treatment period

not really like the approved treatments as they usually look for
a cure and complain about necessity to continue the treat-
Table 2. Clinical trials evaluating efficacy and safety of bimatoprost for the treatment of eyebrow hypotrichosis.

ment for life. Most patients consider topical minoxidil a very

vehicle-controlled study
Study design

old and somehow scarcely effective treatment and don't like

to apply daily a solution that makes the hair sticky and
controlled study

unclean. Patients are afraid of possible side effects of oral

finasteride, and again don't like the idea of taking an oral
medication continuously.
up

PGs are very important in the modulation of hair growth

and PGE2 and PGF2a analogs/agonists are the new possible
To assess the efficacy and safety of bimatoprost 0.03%

Carruthers et al. 2016 [56] Evaluate the safety and efficacy of bimatoprost 0.03%

treatments of alopecias.
Efficacy parameter: investigator-assessed GEBA scale
solution for treatment of eyebrow hypotrichosis
Efficacy parameter: investigator-assessed eyebrow

Bimatoprost will likely be the third medication to be

approved by FDA in the fight against hair loss. The question
in subjects with eyebrow hypotrichosis

is how effective is this new treatment, which will probably be

more expensive than the ones we have, as compared with
topical minoxidil. Another question is about the vehicle of the
solution, as this is a very important factor for patients compli-
Aim

ance. Propylene glycol (PG), which is a main ingredient of the

topical minoxidil solutions, causes irritation and itching, and
makes the treatment poorly accepted by the patient. We do
not have information on bimatoprost solution ingredients;
appearance

hopefully PG is absent or present at very low concentration,

or published data on bimatoprost efficacy on the scalp.
GEBA: Global Eyebrow Assessment.

However, if we look at results of phase II clinical trials, reported

on clinicaltrials.com, efficacy does not look superior to topical
minoxidil. The phase III clinical trials only involve AGA in men,
Beer et al. 2013 [55]

as after results of phase II clinical trials in female pattern hair

loss, Allergan decided not to start phase III clinical trials in
women. This is unfortunate as females represent a great pro-
portion of patients who consult our hair loss clinics.
Bimatoprost is the only approved treatment for hypotricho-
Trial

sis and alopecia of the eyelashes regardless of its etiology.


Other PG analogs such as latanoprost and travoprost are also
effective even if not approved and patients can utilize the
ophthalmic solutions that are available worldwide. The
ophthalmic solutions of bimatoprost can also be utilized in
countries where bimatoprost is not approved for this indica-
tion. Eyelashes hypotrichosis is more a cosmetic than a med-
ical need in most cases, as data on bimatoprost efficacy in AA
are still controversial. However, PG analogs and agonists are
the only therapeutic option for the eyelashes as vehicle of
topical minoxidil contains alcohol and is not suitable for this
delicate area. Eyebrow hypotrichosis due to AA or frontal
fibrosis alopecia can also possibly benefit from these
medications.
Funding
This paper was not funded.
Declaration of interest
A. Tosti has acted as; a consultant for DS healthcare (USA) and P&G (USA);
an investigator for Incyte (USA) and has received royalties from Karger
(Switzerland), Springer Verlag, (Germany); Taylor and Francis (UK). The
authors have no other relevant affiliations or financial involvement with
any organization or entity with a financial interest in or financial conflict
with the subject matter or materials discussed in the manuscript apart
from those disclosed.
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