Oral Tranexamic Acid for Melasma — Mechanism, Duration, Cautions

Three-line summary

• Tranexamic acid is a hemostatic drug by origin. It came into melasma treatment once it emerged, well after the fact, that the plasmin it suppresses is also involved in the pathway that stimulates melanocytes. In Korea it is a prescription-only medicine licensed for hemostatic use alone, so using it for melasma is prescribing outside the licensed indication.
• Taking it orally is not a treatment that erases pigment already on the skin. It is a treatment that holds down the return of pigment. A Korean study reported better results when it was run together with toning than with toning alone, and the 2023 meta-analysis also reported a significant effect. Its place is alongside lasers and topical depigmenting agents.
• The effect generally shows from around one to two months in, and there are reports that relapse appeared more readily where the course was short. But it is not advised where there is a thromboembolic history, anticoagulant or oral contraceptive use, pregnancy or breastfeeding, smoking, or heart disease, so please do not obtain it and take it on your own judgment — the history has to be checked in consultation first.

Why a drug that stopped bleeding ended up being used for melasma

Melasma is a common pigmentary condition. It is a chronic change in pigment that settles on the face, particularly the cheeks and forehead, the nose and the bridge of the nose, and it is common enough to be seen in roughly one person in ten. Ask most people how melasma is treated and lasers come to mind first, and in practice, topical agents aside, lasers do take the largest place in treatment. For some years now, though, the literature on melasma treatment has featured an oral drug that never drops off the list. The ingredient on the first line of that list is tranexamic acid.

How it arrived in melasma treatment was not planned. The first confirmation that tranexamic acid worked on melasma goes back to 1979. In the course of trying the drug for urticaria, a researcher happened to observe that a patient's melasma faded alongside. The effect was not known first and then applied; the effect was seen first and the reason was looked for afterwards.

Studies that followed the question of why it worked then accumulated, the pathway was explained piece by piece, and it is now an ingredient that no account of the drug treatment of melasma leaves out. That it started from a chance observation and had its mechanism explained only later is worth pausing on once when you are getting to grips with this ingredient. Because this was never a drug designed to target pigment from the start — it is a drug used for another purpose that turned out to overlap with the pigment pathway — the contraindications we come to later arise from conditions on the blood side, which have nothing to do with pigment.

There are broadly three oral drugs used in melasma

Look through the review papers on melasma treatment and the oral section is generally made up of three items.

• Tranexamic acid — the ingredient placed at the very front among the oral options.
• Polypodium leucotomos — mentioned alongside it, in the oral antioxidant group.
• Glutathione — likewise in the oral antioxidant group.

A 2017 melasma review shows the same arrangement, putting tranexamic acid first and offering the other two as alternatives. The three are not set side by side with equal weight; there is an order to them, according to how much evidence has built up. So when the oral options come up, tranexamic acid is the axis, and the antioxidants are more often placed alongside it, or carried on in the maintenance phase once tranexamic acid has been stopped.

In Korea it is still a drug licensed as a hemostatic

There is a point here that has to be made plainly. Evidence accumulating and a licence changing are two different things. In Korea, tranexamic acid is a prescription-only medicine licensed for hemostatic use alone. Prescribing it for melasma therefore means using it outside the licensed indication, and it falls outside national health insurance cover. It also means that, however many studies report an effect in melasma, formal approval for a pigmentary condition has not yet been reached.

In Korea the same ingredient reaches the market along two routes: prescription-only medicines, and over-the-counter products that can be bought without a prescription. The latter combine tranexamic acid with ingredients such as ascorbic acid, calcium pantothenate, L-cysteine and pyridoxine hydrochloride. Among these, vitamin C and L-cysteine are known to affect blood glutathione levels, so the combination can be read as one designed with pigment in mind.

But being able to buy something and it being fine to take are two different statements. We will set this out in detail further on, but the ingredient carries clear contraindications tied to clots and emboli, and there are points at which it becomes entangled with other medications being taken. The over-the-counter form also has a course length set at up to two months on the product information, which leaves a gap against the period we would hope for in melasma. These are areas that are hard to judge for yourself, so it is safer to start after your history and current medications have been checked in consultation.

A single substance, plasmin, connects hemostasis and pigment

To understand why a hemostatic drug acts on pigment, the quickest route is to follow one substance: plasmin. It originally appears in the process by which blood clots, and it later emerged that it is also bound up with melanin. This substance is the bridge between the two stories.

First, the hemostasis side

When the body is injured, clotting factors are released from platelets and the damaged vessel wall, and those factors form fibrin, which builds a mesh so that the blood clots. If that mesh kept being made without limit, clotting would never stop, so the body also keeps a pathway that breaks fibrin down ready for the opposite purpose. The substance that carries out that breakdown is plasmin.

Tranexamic acid binds to plasminogen, the stage before plasmin, and blocks the process by which plasmin reacts with fibrin and breaks it down. The fibrin does not dissolve, so the bleeding stops. Because it blocks fibrinolysis it is called an antifibrinolytic, and this is exactly the hemostatic drug we know.

That plasmin turned out to have another face

Plasmin, which was thought to work only in hemostasis, was later found to be related to melanin as well. What is known comes down to two things.

• It promotes the growth of melanocytes — through b-FGF, it acts to activate the cells that make melanin.
• It promotes the production of arachidonic acid — arachidonic acid is a substance that promotes melanin production.

And for the mechanism by which melasma arises and worsens, there is a proposed hypothesis that ultraviolet light raises the activity of plasmin in keratinocytes, which stimulates melanocytes, and melanin increases as a result. The exact mechanism by which melasma appears and deteriorates has not been fully worked out, but follow this hypothesis and it becomes clear where tranexamic acid intervenes. It cuts into the middle of the chain that runs ultraviolet light to plasmin activity to melanocyte stimulation to more pigment.

It also acts on the vascular side

On top of this, tranexamic acid is known to act in the direction of holding down new vessel formation, by suppressing VEGF and endothelin-1. What this means in melasma is not small. Melasma is not a matter of pigment alone; it is a change produced by three things tangled together — keratinocytes, fibroblasts and vascular endothelial cells. This vascular component is part of why melasma with a red cast running through it can feel particularly slow to treat.

The direction of melasma treatment has shifted along these same three axes. It used to focus on keratinocytes and melanocytes, with treatment aimed mostly at taking pigment out directly, and the toning lasers represented that position. More recently the weight given to fibroblasts and the dermal environment has grown, so treatments that address the dermis — radiofrequency, Genesis, picosecond fractional, microneedling RF — come in alongside. Oral tranexamic acid, within this picture, can be understood as a drug that intervenes at two of these places at once: the pigment pathway that starts in the keratinocytes, and the vascular side.

It is not in competition with lasers; the roles are different

When the oral drug comes up, people often ask whether that means they could take the tablet instead of having the laser. To give the conclusion first: no. The two treatments have different jobs, so they are not substitutes for one another.

Melasma treatment is easiest to follow if you divide it broadly in two.

Neither side resolves things on its own. Attend only to the holding-down side and you help with prevention while the pigment you can see now stays exactly as it is; repeat only the taking-out side and you cycle through improving and rising again, with time and cost mounting all the while. This is why treatment runs more smoothly when both axes are carried together.

What has been reported when it is run alongside toning

Among Korean studies there is a report that the group having toning together with oral tranexamic acid showed significantly better results than the group having toning alone. The structure is that a drug which holds down the pathway making pigment again is laid on top of the change produced by treatment acting on pigment directly.

There is also material showing the breadth of the evidence. A meta-analysis published in 2023 pooled 28 randomized controlled trials and concluded that tranexamic acid showed a significant effect in melasma. The same paper added, however, that the topical form and the form injected into the lesion need further evidence. In other words, the form with the thickest evidence behind it is the oral one.

Setting out what we hope for in practice: compared with running a laser on its own, change tends to appear a little earlier, the number of sessions needed to reach the same result tends to fall, and it also works in our favor during the maintenance phase once things have improved to a degree. These tendencies do not show to the same extent in everyone, and they vary from person to person.

So melasma treatment now uses several axes together

From the older approach of simply repeating toning, we have moved toward placing topical depigmenting agents, the oral drug, and treatments addressing the dermal environment alongside one another. For topical agents we use hydroquinone, a triple-combination formulation, or a retinoid depending on the situation, and for sun protection we tend to advise a tinted formulation that accounts for visible light and not ultraviolet alone. Peels kept within a moderate range and pigment lasers are added to that, and the oral drug takes the position of holding down relapse in the background.

There is one thing to watch when peels or resurfacing are used alongside. Melasma is a pigment that reacts sensitively to irritation, so overdoing it can push the pigment darker instead. This is why turning up the intensity to clear pigment faster works particularly poorly in melasma, and it is also the background to the arrangement that lowers the intensity and carries the holding-down axis alongside instead.

Judged by cost and time the conclusion is much the same. Repeat pigment lasers alone while chasing a course that improves and rises again, and the number of sessions keeps climbing. Attend to the axis that holds down relapse as well, and the sessions needed to reach the same result tend to fall, while maintenance afterwards tends to be easier. The reason an arrangement using both axes is advised has to do not only with the effect but with the burden of the whole course of treatment.

How long it is taken, and what happens when it is stopped

Duration is the question that comes up most often in consultation. We cannot set a specific single dose or a number of times per day for you in an article like this. It is a prescription-only medicine, the strength differs between products even for the same ingredient, and above all there is a history that has to be checked before the first tablet. On the period and the course, though, the studies do give us a shape.

How long before the effect is felt

It generally takes one to two months for a change to appear. Judging it a few weeks after starting is therefore early. Material pooling several studies has proposed 12 weeks, that is around three months, of treatment as a baseline, and in practice we often take about three months as one block. Depending on the situation it is sometimes carried on longer than that, up to nearly a year.

Stopping can let it rise again

Melasma is a pigmentary condition whose cause does not go away. Ultraviolet light keeps landing on the skin, and hormonal influence continues. Release the pressure and there is room for the pigment to rise again. Research has also reported that relapse appeared more readily where the course had been short. This is why taking it for two or three weeks, seeing no change and giving up is not an approach we advise.

Nor is it a drug that can simply be continued indefinitely. It is a prescription-only medicine, and the form that can be bought without a prescription has a course length set at up to two months on its information leaflet, so there is a limit to how far the period can be stretched. In practice, then, rather than dragging out the course itself, we set the point at which it stops and the plan that follows together.

The plan is built on the assumption that it stops

• Topical first, the tablet later — manage with topical depigmenting agents and sun protection first, and add tranexamic acid for a set period when the response is not enough. An arrangement that uses only as much as is needed.
• Together from the start, maintenance after stopping — begin with an antioxidant and tranexamic acid together early on, then stop the tranexamic acid once it has been taken for long enough while continuing sun protection and the antioxidant. An arrangement that moves into a maintenance phase which keeps deterioration at bay.

The pattern we most often see in consultation, and regret, is taking it briefly and stopping, over and over. A few weeks of it, no change, stop; the pigment becomes noticeable again, another short spell. This drug takes time to show an effect, and relapse has been reported to appear more readily the shorter the course, so an approach like this makes it hard to get the share of the work the drug could actually take on. It is better to decide at the outset how long a period you will give it.

Either way, the common point is that the moment the drug stops is not the end of treatment. The holding-down role the drug had been carrying has to be designed to pass to sun protection and maintenance, and only then can you reduce the situation where pigment comes back quickly after stopping. That is why we talk about the stopping point at the same time as starting.

When it should not be taken — this is the most important part

This is the first thing to check when handling this drug. Tranexamic acid acts in the direction of blocking the breakdown of fibrin. For most healthy adults that is not a problem, but where there is already a clot, or a raised risk of one forming, that same direction can work against you. So in the cases below, it is better not to take it if at all possible.

• Where there is an allergy to tranexamic acid
• Where there is intracranial hemorrhage
• Where there has been a clot in a vein or an artery — past history is included.
• Where there is current thromboembolic disease
• Where an anticoagulant is being taken
• Where an oral contraceptive is being taken
• Where the patient is pregnant or breastfeeding
• Smokers
• Where there is heart disease — arrhythmia, angina and the like.

Why oral contraceptives are on the list

Oral contraceptives are on this list for two reasons. One is that the contraceptive itself is known as a factor that aggravates and triggers melasma. Melasma often appears in connection with pregnancy or hormonal change, and among medications the contraceptive is counted an aggravating factor along with anticonvulsants and photosensitizing drugs. The other concerns clot risk, which is why combining it with a drug that blocks fibrinolysis is not advised.

So if you are on an oral contraceptive, the first thing to establish is not whether to add tranexamic acid but whether that drug is sitting in the background of the melasma. Please tell us about every medication you are taking during the consultation.

If surgery or a hospital stay is scheduled, you must tell us

Circumstances sometimes change after the course has begun. Surgery is planned; a hospital stay or recovery period arrives that means lying down for long stretches; a schedule comes up in which moving about for a long time is difficult. These situations border on the risk on the clot side, so you should tell us in advance that you are taking it, and we decide in consultation whether to continue or pause. If you are having a procedure or an operation under another specialty, it is also better to mention that you are taking this drug.

To sum up, for most healthy adults this is a drug unlikely to cause much trouble, but that judgment has to be made after checking your history and current conditions, before the course begins. Keep to that order and you can take the effect on the pigment side while avoiding trouble from the drug. This is the single biggest reason we do not advise obtaining it and taking it yourself without a prescription.

Reported adverse effects, and the amounts actually used

The reported adverse effects include abdominal pain, nausea, vomiting, numbness in the hands and feet, itching of the face, tinnitus, tremor, menstrual irregularity, hair loss, facial hypertrichosis, swelling of the lips or around the eyes, and palpitations. The list alone feels long, but these do not appear in everyone and they are very infrequent.

There is one more thing worth reading alongside. The adverse effects listed above were mostly reported at the amounts used when this drug is given as a hemostatic. The amount used in melasma treatment comes to about one sixth of the amount used for hemostatic purposes. The same ingredient is used at a different order of magnitude, so there is no need to transpose the reported list onto melasma treatment and worry about it as it stands.

Infrequent is not the same as absent, though. If a symptom out of the ordinary appears while you are taking it, please do not put up with it or adjust the amount yourself; it is safer to stop and have it checked in consultation. In particular, if a symptom arises that could suggest a clot — a swollen leg, pain on one side only, sudden breathlessness or chest pain — you should be seen without delay.

What about the topical and injected forms

Besides the oral form, tranexamic acid has also been tried as a topical and as a form delivered directly into the skin. The amount of evidence behind each differs, though.

Topical tranexamic acid

There are studies reporting that liposomal formulations at 2% and 5% were effective when used for two to three months. In another study, 3% tranexamic acid was reported to show an effect similar to a cream combining 3% hydroquinone with 0.01% dexamethasone. The periods of use put forward run to roughly 5 to 18 weeks.

The form delivered directly into the skin

Injecting directly into the skin is not a licensed route of administration. In practice the injectable preparation is diluted to a low concentration, and two approaches are used alongside one another: applying it and then making channels with fine needles so that it is absorbed, and injecting it in directly. One study reported improvement in melasma when it was carried out over 8 to 12 weeks, but redness and pain at the injection site were noted as a problem. Which approach is better is also disputed, with studies reaching different conclusions.

The advantage of this route is that a small amount can be delivered comparatively precisely to the place it is wanted; the drawback is that pain or discomfort can carry on for two or three days. There is a claim that applying it and then driving it in by iontophoresis works well without pain, but there is not yet research to support that.

Ranking the three forms by how much evidence has accumulated gives oral, then injection or delivery using fine needles, then topical. The oral form does carry the constraint of being hard to continue over a long period, so where a contraindication makes taking it difficult, or where extending the course further is awkward, the other forms can be considered as an alternative. ABLE Dermatology also offers a melasma injection that mixes in tranexamic acid and delivers it into the skin, but we use it while making clear that this route does not have the accumulated evidence that the oral form does.

For pigment other than melasma

Reviews covering hyperpigmentary conditions other than melasma set out that tranexamic acid is a drug that helps in several pigmentary conditions, but that more randomized controlled trials and case-control studies are still needed. Specifically, they carry accounts of it helping in Riehl melanosis and of an effect in post-inflammatory hyperpigmentation as well.

There is one point worth noting, however. When used together with a laser, a preventive effect on post-inflammatory hyperpigmentation has been reported as not confirmed. Which is to say it is hard to expect it to serve as something taken in advance to stop pigment rising after a laser. For reducing pigment after a laser, sun protection, managing irritation and adjusting the intensity of the treatment come first.

In short, it can be tried in other pigmentary conditions such as post-inflammatory hyperpigmentation, Riehl melanosis or lichen planus pigmentosus, but it is right to judge with the caveat that the research has not built up the way it has in melasma. Where it is used for pigment other than melasma, we tend to set a shorter period and watch the course.

Where this drug sits at ABLE Dermatology

What we establish first in consultation is not whether to use the drug but what kind of pigment it is that we are looking at. Melasma is divided by distribution into centrofacial, malar and mandibular patterns, and by the depth at which the pigment sits into epidermal and dermal types. On top of that we look at how much red cast, that is vascular component, is mixed in. Where these three differ, the treatment plan differs, even for the same melasma.

Next comes the history and the medications being taken. We sort out whether any of the contraindications set out above apply, and only then judge whether to prescribe. It is not an order that settles on the drug from the pigment alone.

The side that acts on pigment directly

• Hollywood Spectra toning — used to address superficial blemishes and overall tone.
• PicoPlus pico toning — picosecond delivery, used for melasma and blemishes including cases where conventional toning caused an adverse effect.
• Dual toning — two devices combined, for when superficial and dermal pigment have to be addressed together.
• Pico fractional, Potenza, Density — placed where the dermal environment, that is the fibroblast side, needs addressing alongside the pigment itself.
• V-Beam Perfecta — used where redness and a vascular component are present as well.
• Various peels and LDM — peels kept within a moderate range tidy up the keratin layer and the tone, and skin left sensitive after a procedure is calmed with LDM.

When a contraindication makes taking it difficult

Where the consultation establishes that a contraindication applies, the drug comes out of the plan. That does not leave us without a way to treat. In this case we fill the holding-down axis with something other than the drug. Sun protection that accounts for visible light is set more strictly, the weight given to topical depigmenting agents and oral antioxidants goes up, and whichever aggravating factors can be adjusted are dealt with first.

The plan on the pigment-removal side changes too. Packing in strong treatments while the holding-down axis is weak tends to be followed quickly by relapse, so rather than raising the intensity of any one session we choose an approach that adjusts the intervals and the number of sessions and proceeds gently. Where the condition is temporary, as with pregnancy or breastfeeding, we sometimes build the plan again once that period has passed. Contraindications can change over time, so we check them again as the course goes on.

The side that holds down the return

This is where oral tranexamic acid goes. Placed alongside it are sun protection that accounts for visible light, topical depigmenting agents, and in some cases an oral antioxidant. It is not a structure in which one drug settles the melasma; it is closer to the reality to understand it as the role of protecting the result that the pigment-removing treatment has produced.

When the course begins we set the period, the stopping point and what will be carried on afterwards, all together. Melasma is a pigmentary condition that follows a course of improving and then rising again, so rather than repeating lasers alone and chasing relapse, an approach that carries the holding-down axis and the taking-out axis together tends to be less of a burden in time and cost as well. The degree of response and how long it holds do vary from person to person.

One last word. Tranexamic acid is a prescription-only medicine that requires a consultation and a prescription, and it is a drug with clear contraindications related to clots. Please do not obtain it privately and start taking it on the strength of having heard it is good for melasma; we advise deciding whether to start, and for how long, after your history and current medications have been checked.

From consultation to procedure

A board-certified dermatologist examines you directly, identifies the layer the cause sits in, decides the device and the parameters, and the same dermatologist carries on to perform the procedure. This is not a structure in which a consultant recommends the treatment.

Sessions, intervals, maintenance timing and cost are agreed together before the first procedure.