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Product Review

Use of tranexamic acid for skin whitening and


melasma therapy: Aproduct review
Halimi Syafiqah Nadiah1, Masood Hannah2, Kah Seng Lee3, Suhaidah Mohd Jofrry1,4, Long Chiau Ming1,4
Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam, 4Vector-borne Diseases Research Group (VERDI), Pharmaceutical and Life Sciences
CoRe, Universiti Teknologi MARA, Shah Alam, Selangor, 2Department of Pharmacy, Hospital Tuanku Ampuan Najihah, Negeri Sembilan, Malaysia,
3
School of Pharmacy, Curtin University, Perth, Australia
1

Address for correspondence:


Halimi Syafiqah Nadiah,
Level 11, FF1 Building, Faculty of
Pharmacy, Universiti Teknologi MARA,
Puncak Alam, Selangor, Malaysia.
Email:syanadia23@gmail.com

Key words: Malaysia, nonprescription


medications, selfmedication,
tranexamic acid

ABSTRACT
Purpose: The aim of this study is to assess the usage of tranexamic acid as skin whitening
and melasma therapy.
Methodology: An electronic search on PubMed, MEDLINE and Cochrane Library with
keywords tranexamic acid, oral, systemic, whitening, lightening, and melasma
was carried out. The literatures are summarized in the evidence tables. Further search
on PBAC, UK, NFSA, SMC, CEDAC, MIMS, and Micromedex was performed for listing
reviews of tranexamic acid.
Results: The data available are not scientifically proven to demonstrate the role of
tranexamic acid as an effective treatment for melasma therapy and whitening agent.
Conclusions: As a conclusion, due to the lack of data, it was not possible to reach
a conclusion on the use of tranexamic acid as cosmetic products, especially with
systematic usage.

INTRODUCTION
Tranexemic acid is a competitive inhibitor of plasmin
activation, commonly used as a hemostatic agent due to
its antifibrinolysis action is also promoted as a systemic
skin whitening agent particularly as oral or intradermal
injections for melasma. Tranexamic acid has become
a phenomenon in Malaysia as skin whitening and
melasma therapy. Tranexamic acid capsule and can be
bought at online resellers without valid prescription.

MALAYSIAN MEDICINE ADVERTISEMENT


BOARD GUIDELINES
According to Medicine Advertisement
Board(MAB), [1] any advertisements published
Access this article online
Quick Response Code:
Website:
www.archivepp.com
DOI:
10.4103/2045-080X.183037

2016 Archives of Pharmacy Practice | Published by Wolters Kluwer - Medknow

should have information that is accurate, balanced,


be capable of substantiation, fair, informative,
objective, reliable, truthful, unambiguous, and
uptodate.
Advertisements published should not contain any
misleading or unverifiable information either directly
or by implication that is likely to induce unjustifiable
medical use or to give rise to undue risks. It is also
important that advertisements do not exploit the lack
of knowledge and abuse the trust given by the general
public. Any approved advertisements by MAB must
display KKLIU number. The name, address, and
contact number of the advertiser must be clearly stated
on the page.
This is an open access article distributed under the terms of the Creative
Commons AttributionNonCommercialShareAlike 3.0 License, which allows
others to remix, tweak, and build upon the work noncommercially, as long as the
author is credited and the new creations are licensed under the identical terms.
For reprints contact: reprints@medknow.com

How to cite this article: Nadiah HS, Hannah M, Lee KS, Jofrry SM,
Ming LC. Use of tranexamic acid for skin whitening and melasma
therapy: A product review. Arch Pharma Pract 2016;7:S43-7.

S43

Nadiah, etal.: Tranexamic acid as a cosmeceutical

MAB prohibit the advertisement of controlled


medicine, poison, and products containing poison
pursuant to schedule 1 of the Malaysian Poison Act
1952 unless it is specifically exempted.
Testimonials can be included in the advertisements.
However, the individual who provides the testimony
must genuinely exist and responsible. The individual
must also be accountable to the advertisement and the
testimonials given as per say of the indications being
approved. Advertisements with testimonial must
display the statement: The effect of the product may
vary among individuals.
Any claims regarding the advertised products
must be based on the updated evaluation of all
evidence and must reflect the evidence accurately
and clearly. References of this substantial evidence
must be included. All claims should be capable
of substantiation either by reference to approved
labeling or by scientific evidence from scientifically
proven investigations. Such evidence must be readily
available and can be reproduced on request.
Hyperboles claims cannot be used to imply or claim or
infer the superiority of the advertised product. General
public should not be led to overestimate the value of
the product by exaggeration or unrealistic claims
or statements made by advertisers. Advertisements
should not contain exaggerated, improper and
misleading claims or visuals to show changes in the
human body.
Care should be given to ensure all claims used are
related to the approved indication and the degree of
severity for which the product is indicated. Claims
that the products are free from any side effects should
not be implied inside the advertisements.
Even though there are strict and comprehensive
guidelines by MAB on advertisements, internet
resellers whom selling tranexamic acid capsule
illegally never comply with any of these guidelines.
Resellers claimed that tranexamic acid can become
such a supremacy whitening agent with the false
testimonial and hyperboles claiming. There is clearly
no KKLIU number and there are no enough data
to show the effectiveness of oral tranexamic acid in
treating melasma and hyperpigmentation. Putting the
illegal advertisement of TransCap on the internet and
publicize it to the general public are clearly against
the MAB law.

S44

METHODOLOGY
An electronic search of PubMed, MEDLINE and
Cochrane Library using the following criteria were
carried out [Table1].

Efficacy and safety


A clinical trial study was conducted by Na et al.
with 25 women for 8 weeks in Seoul, South Korea.
Volunteers were instructed to take 250mg tranexamic
acid tablets three times a day and apply a tranexamic
acid topical agent twice a day for 8weeks. This study
found out that tranexamic acid will reduce epidermal
pigmentation that related with melasma and also
reversed melasmarelated dermal changes, such as
vessel number and increased numbers of mast cells.[2]
A clinical trial study carried out by Wu etal. enrolled
74 volunteers in China. Tranexamic acid tablets were
prescribed at a dosage of 250mg twice daily for a
therapeutic period of 6months. All the volunteers
were monitored for more than 6months after the
treatment. The effects of treatment were evaluated
by two physicians independently and by the patient
based on the improvement of pigmentation and
reduction in melasma size. The study concluded that
oral administration of tranexamic acid is an effective
and safe therapy for the treatment of melasma.
However, further research on the longterm usage of
tranexamic acid is needed(level evidence II).[3]
Preliminary clinical research was studied in Beijing,
China with a total number of 35 melasma patients.
The total duration of the study was 16weeks. After
evaluation of the testing results, patients were asked
to take two tablets of 250 mg tranexamic acid after
meal, three times a day for 16 weeks. The patients
were advised to avoid excessive sun exposure and to
apply the same broadspectrum sunscreen with a sun
protection factor 30. The study concluded that oral
compound tranexamic acid is a potentially new and
Table1: Search criteria and results
Criterion

Search result

Key words used

Oral, systemic, tranexamic


acid, tren, transamin,
transcap, melasma, whitening,
lightening, hyperpigmentation
Humans
All
13
5
13

Filters
Years searched
Total number of articles reviewed
Relevant full text articles reviewed
Relevant abstracts reviewed

Archives of Pharmacy Practice Vol.7 Supplement 1 2016

Nadiah, etal.: Tranexamic acid as a cosmeceutical

promising therapeutic option. However, a largescale


and multicenter study will be needed to define its
longterm benefits and any potential additional
adverse effects.[4]
A prospective, interventional, randomized controlled
trial was conducted among 260 melasma patients in
Nepal. Patients were divided into two groups, control
group and intervention group. Each group consists of
130patients. First group(GroupA) was given routine
treatment measures and oral tranexamic acid whereas
second group(GroupB) was treated only with routine
topical measures. Capsule tranexamic acid was
prescribed at a dose of 250mg twice a day for 3months
and cases were followed for 3months. The response
was evaluated on the basis of melasma assessment
severity index(MASI). Mean scores between the two
groups were then compared. Statistically, significant
decrease in the mean MASI from baseline to 8 and
12 weeks was observed. The study then suggested
that addition of oral tranexamic acid provides
rapid and sustained improvement in the treatment
of melisma. However, it is not safe to use it for a
long period in view of its antihemorrhagic property
causing side effects such as cerebrovascular accidents,
myocardial infarction, pulmonary embolism and
venous thromboembolism. It is contraindicated in
patients with acquired defective color vision, an active
intravascular clotting condition, and hypersensitivity
to tranexamic acid.[5]

POTENTIAL RISK TO GENERAL


POPULATION
Tranexamic acid was listed under Group B inside
Malaysian regulatory classification. [6] GroupB
medicines can only be prescribed by a registered
medical practitioner, dentist, or veterinary surgeon,
as the case may be and with the prescription in the
correct form as required by the law.
This means tranexamic acid can only be sold with
a valid prescription from a registered medical
practitioner, dentist, or veterinary surgeon. However,
tranexamic acid, a prescription drug is sold to the
general public without any valid prescription and
supervision from medical healthcare through online.
Such action can result in various adverse effects as the
usage of tranexamic acid is not being monitored by
licensed medical practitioners and can be fatal.
Even though tranexamic acid is already registered
in Malaysia as a poison B prescription drug, the
Archives of Pharmacy Practice Vol.7 Supplement 1 2016

approved indications are for hemorrhage associated


with excessive fibrinolysis and abnormal bleeding.
Atranexamic acid indication as melasma therapy
is not approved, and there are not enough scientific
data and clinical trials that can support the use
of oral administration of tranexamic acid as a
whitening agent and melasma therapy for the
publics interest.[7,8]
Tranexamic acid with its antihemorrhagic
property, if being used for long duration can result
in side effects such as cerebrovascular accidents,
myocardial infarction, pulmonary embolism, and
venous thromboembolism.[6] Tranexamic acid is
contraindicated in patients with active intravascular
clotting condition, acquired defective color vision,
thromboembolism, cerebral edema and hypersensitive
to tranexamic acid. Tranexamic acid concomitant
use with combination hormonal contraceptives
can increase the risk of thromboembolism and
thrombosis.[9]
The usage of tranexamic acid has been associated
with visual disturbances including impaired color
vision, visual impairment, and blurring of vision. For
patients who are to be treated with tranexamic acid for
several weeks, an ophthalmic checkup is advisable,
if possible, before treatment is initiated and regularly
during treatments. Patients with irregular menstrual
bleeding should not use tranexamic acid until the
cause of the irregularity has been establish.[8,9]
The safety issues and contraindication were not
highlighted by the internet resellers. Claims that
Tranexamic acid is safe to be used for all ages and
pregnant women are plain hubris. This illegal trend
of selling tranexamic acid freely in social network,
especially Facebook and Instagram without proper
consultation or medical investigation from medical
practitioners is illegal and unaccepted.
The recommendations for tranexamic acid are listed
in Table2.
CEDAC has four different types of recommendations:
(1) Unrestricted listing,(2) list in a manner similar to
other drugs in the class,(3) list with criteria,(4) do
not list.
PBAC makes four types of recommendations
(1) unrestricted listing,(2) restricted benefit,
(3) authority required(the equivalent of prior
approval),(4) do not list.
S45

Nadiah, etal.: Tranexamic acid as a cosmeceutical

Table2: Recommendations
Body/country

Drug: Tranexamic acid

Recommendation/reason

CEDAC, Canada

CEDAC registered
tranexamic acid in
February 2, 1983

PABC, Australia[9]

Tranexamic acid was


registered by Therapeutic
Goods Administration
(TGA) in the year 1971

MHRA, United
Kingdom

Medicines and Healthcare


products Regulatory Agency
registered tranexamic
acid in August 07, 1972
Reregistration:
November 1, 2001
The Norwegian Food Safety
Authority approved as facial
mask and facial cream 3%
in 2012

Hereditary angioneurotic oedema


Increased local fibrinolysis when the diagnosis is indicative of hyperfibrinolysis, as with
conization of the cervix, dental extraction in patients with coagulopathies(in conjunction
with antihemophilic factor) epistaxis, hyphema, and menorrhagia(hypermenorrhea)
Tranexamic acid 500 mg are currently register for the indications
Hereditary angioneurotic edema
Shortterm use in the treatment of hyphemia and in patients with
established coagulopathies who are undergoing minor surgery
Menorrhagia
Local fibrinolysis: For shortterm use in prophylaxis and treatment in patients at high
risk of periand postoperative hemorrhage following: Prostatectomy, conization
of the cervix, surgical procedures and dental extractions in hemophiliacs
General fibrinolysis: Hemorrhagic complications in association with
thrombolytic therapy, hemorrhage associated with disseminated intravascular
coagulation with predominant activation of the fibrinolytic system
The Norwegian medicinal products agency considered tranexamic acid a medicinal
remedy. Because of that up till 2008 topical products containing this substance was
considered medicinemeaning a topical product containing it as automatically
classified a medicine. Applications for allowance to use the substance for other
purposes(cosmetics) were rejected. This regime has since been lifted
The NFSA consider tranexamic acid is safe for use in face cream and facial mask at a
concentration of 3%, but should be prohibited in all other cosmetic products

NFSA, Norway[8]

CONCLUSIONS
The need for white and fair skin is a worldwide
phenomenon, and it is greatly exploited by both the
cosmetic and dermatologic industries.
Topical use of tranexamic acid has been used as a
skin whitening agent in numerous leaveon products
since 2002, although to which degree is currently
unidentified.[8] Use of oral administration of tranexamic
acid for melasma therapy has been studied, mostly in
Asian countries and even though results from these
studies show positive results, there is not enough
controlled study and randomized clinical trials were
done, especially in other ethnics group for example,
Africans and Caucasians that will reflect the world
population. The data available are not scientifically
proven to demonstrate the role of tranexamic acid
as an effective treatment for melasma therapy and
whitening agent.
The safety for the use of tranexamic acid in cosmetic
products has been examined by the Council of
Europe.[10] It was concluded that due to the lack of
data it was not possible to reach a conclusion on the
use of tranexamic acid in cosmetic products, especially
with systematic usage.
Therefore, firm regulations should be imposed to
prohibition the use of these agents until wellconducted
randomized controlled trials are available ensuring the
safety and efficacy of these agents. Internet resellers
S46

that are selling prescription drugs should be brought


to justice.

Financial support and sponsorship


This work was supported by Research Acculturation
Grant Scheme: RAGS/1/2014/SKK07/UITM//7.
The authors would like to express their gratitude
to Ministry of Higher Education and Universiti
Teknologi MARA (UiTM), Malaysia for financial
support for this research.
Conflicts of interest
There are no conflicts of interest.

REFERENCES
1. Ministry Of HealthM. Guideline on Advertising of
Medicines and Medicinal Products to General Public:
Medicine Advertisements Board in MAB; 2015.
2. NaJI, ChoiSY, YangSH, ChoiHR, KangHY, ParkKC. Effect
of tranexamic acid on melasma: A clinical trial with
histological evaluation. JEur Acad Dermatol Venereol
2013;27:10359.
3. WuS, ShiH, WuH, YanS, GuoJ, SunY, etal. Treatment
of melasma with oral administration of tranexamic acid.
Aesthetic Plast Surg 2012;36:96470.
4. LiY, SunQ, HeZ, FuL, HeC, YanY. Treatment of melasma
with oral administration of compound tranexamic acid:
A preliminary clinical trial. JEur Acad Dermatol Venereol
2014;28:3934.
5. KarnD, KcS, AmatyaA, RazouriaEA, TimalsinaM.
Oral tranexamic acid for the treatment of melasma.
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Kathmandu Univ Med J(KUMJ). 2012;10:403.


6. MIMS. Tranexamic Acid; 2015. Available from: http://
www.mims.com/Malaysia/drug/info/Transamin/.
[Last cited on 2015Aug23].
7. NPCB. Tranexamic Acid 250; 2015. Available from: http://
www.portal.bpfk.gov.my/risalah-maklumat-ubat-untukpengguna-rimup/item/transamin-capsule.[Last cited on
2015Aug23].
8. NorwayFSA. Risk Profile Tranexamic Acid; 2012.
Available from: http://www.mattilsynet.no/kosmetikk/

Archives of Pharmacy Practice Vol.7 Supplement 1 2016

stoffer_i_kosmetikk/risk_profile_tranexamic_acid. 9965/
binary/Risk%20Profile%20Tranexamic%20acid.[Last cited
on 2015Sep23].
9. AustralianG. Australian Public Assessment Report for
Tranexamic Acid Department of Health and Ageing:
Therapeutic Goods Administration; 2010. Available
from: http://www.file:///C:/Users/home/Downloads/
ausparcyklokapron%20(1).pdf. [Last cited on 2015 Dec].
10. Europe Co. Active Ingredients Used in Cosmetics: Safety
Survey: Council of Europe Publishing; 2008.

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