Side Effects Of Common Melasma Treatments

Side Effects Of Common Melasma Treatments

As we have discussed in previous blog posts, there are multiple treatment options for melasma that have proven to be effective. A common concern regarding melasma treatments is what side effects, if any, you can expect when using these creams. In this article, we’re going to discuss some of the most common active ingredients used in melasma treatments and their associated side effects.


If you’ve done research into treating melasma, chances are that you have come across hydroquinone before. Hydroquinone is the most common pigment-fading ingredient utilized for melasma with various combinations and concentrations available as both prescription and over-the-counter treatments.

So, what are the common side effects that can be expected when you use hydroquinone?

The first of these is the most obvious: when a cream is used to lighten the color of a pigmented area, there is always the risk that it can work too well and leave an area of pale skin behind. This is also an issue if the hydroquinone is accidentally applied to normal skin next to dark patches.

All things considered, this “side effect” is a good problem for most people who have dark patches of skin. As long as you’re being monitored carefully, as we do at ClearifiRx, your provider can stay up to date with your pigmentation-fading journey and adjust the strength of your hydroquinone to prevent it from going too far. The careful application of hydroquinone cream to only affected areas with skin darkening can also help prevent any surrounding skin from lightening.

Irritation is the next side effect to discuss with hydroquinone, with studies showing that it is the most common adverse effect when using the medication. We know that hydroquinone works by being absorbed into the melanocytes (pigment-producing cells), present in the lower epidermis (outermost skin layer).

Here, hydroquinone blocks an enzyme called tyrosinase which carries out a crucial step in the production of melanin (pigment). Hydroquinone is known to cause irritation as part of its regular mechanism of blocking tyrosinase. This means, in some ways, having a small amount of irritation is to be expected and gives us some reassurance that enough medication is being absorbed into the skin. However, if the degree of irritation goes beyond a small amount of tingling, and instead involves severe redness, burning, or crusting, this may be an indication that the concentration of hydroquinone is too high.

Alternatively, you may be amongst a small set of patients who have an allergic reaction to hydroquinone. In either of these instances, it is important to contact your ClearifiRx provider immediately so that we can evaluate your photos and give you tailored advice on the next steps of your treatment.

The final side effect of hydroquinone is a slightly surprising one. Although most people use hydroquinone for its well-known skin-lightening abilities, using this medication for too long continuously can actually cause the skin to darken, a process known as ‘exogenous ochronosis’. At ClearifiRx, we keep a close eye on the pigment fading regimen our patients are using, in order to make adjustments to avoid any unwanted side effects like this from happening.


Azelaic Acid

Having talked about hydroquinone, the azelaic acid section should be nice and easy. Just as hydroquinone acts as a ‘tyrosinase inhibitor’ in the way we explained earlier, so too does azelaic acid. Azelaic acid is an increasingly popular active ingredient in a lot of cosmetic skin products because of its actions as an anti-inflammatory agent, as well as its ability to help fade pigment.

The main side effect of azelaic acid is mild irritation or drying of the skin. This is unsurprising due to its mechanism as an anti-tyrosinase medication and should prompt concern only if irritation becomes severe, causes peeling, or you experience persistent burning. The mild irritation that is experienced early on with medications such as azelaic acid or hydroquinone often fades away as your skin becomes used to the ingredients. The use of a nourishing moisturizing agent as part of your skincare routine is essential to minimize irritation alongside any treatment regimen.


Tacrolimus may not be a medication you have come across before, but it makes up part of some types of combination treatments alongside other pigment-fading ingredients.

Tacrolimus works by reducing the production of chemical messengers in the body called cytokines. These cytokines normally send signals to the body’s immune system telling it to cause inflammation, but tacrolimus interrupts this signal. Tacrolimus is considered a steroid-sparing agent, meaning that it replaces the steroid creams that would normally need to be used to minimize skin inflammation. As a result, patients can avoid steroid-related side effects such as skin thinning, collagen reduction, and blood vessel prominence.

The most common side effect to be expected with tacrolimus is skin burning or stinging, which occurs in less than 10% of patients. These symptoms normally resolve after a few days of use.

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Tranexamic Acid

Tranexamic acid is a relatively new type of treatment for melasma that can be administered orally in a pill, topically in a cream, or injected. Tranexamic acid works to treat melasma by inhibiting the synthesis of melanin (skin pigment) and preventing the transfer of pigment to the dermis.

For the most part, studies have shown that this type of treatment doesn’t come with many side effects. The side effects of tranexamic acid depend on the way it is administered.

  • Oral TA: Abdominal pain, headaches, nausea, and depression
  • Topical TA: Skin irritation
  • Injection TA: Pain or swelling at the injection site

Melasma Laser Treatment Side Effects

Lasers are a common second-line treatment for melasma. This type of treatment is typically used for stubborn melasma that resists standard first-line treatments, such as topical creams.

The most common side effects that come with laser treatment for melasma are skin irritation, redness, skin peeling, and swelling.
Lasers aren’t right for everyone, as they can actually make pigmentation worse in some people. That’s why it’s important to talk to your dermatologist about your treatment options for melasma and the potential associated risks and side effects.

Chemical Peels Side Effects

A chemical peel is an outpatient procedure that uses a combination of substances to encourage exfoliation and promote the growth of new, healthy skin. Like all types of medical treatments, minor side effects are possible.

The side effects of a superficial chemical peel are much like a sunburn with redness and minor inflammation. These symptoms typically resolve within several days of treatment. The deeper the chemical peel, the longer that they take to heal.

Birth Control Side Effects And Melasma

When it comes to birth control and melasma, it isn’t necessarily that this hormonal treatment has side effects – aside from those that come with the specific medication itself, of course. Rather, it’s important to remember that birth control is a well-known trigger of melasma.

Although scientists don’t know exactly why, yet, elevated levels of estrogen can cause melasma. Hormonal birth control works by increasing estrogen in your body. The result is those dark patches of skin on your face.

Fortunately, melasma can go away on its own if you stop taking hormonal birth control. Diligent sunscreen use and UV protective measures such as avoiding the sun during peak hours (10 am – 2 pm) can help you see fastest results.

Something Is Going Wrong… Right?

When we use any type of new medication, whether it is a tablet or a cream, it’s important to be extra vigilant and pay attention to any symptoms you may experience. It is normal to be concerned if you feel irritation or tingling at the beginning of a new skincare routine, but it does not necessarily mean something is “going wrong”.

As we discussed, when using prescription-strength creams with active ingredients, these medications are absorbed into the pigment-producing cells of the skin and alter the way that they work. This most commonly causes a few days of irritation or tingling as the skin gets used to these new treatments. As long as the side effects do not develop into severe, visible irritation or crusting, they should be seen as proof that you are using active ingredients that are penetrating into the skin cells rather than a sign that things are going wrong.

Brandon Kirsch

Brandon Kirsch, MD, FAAD, is a board-certified dermatologist specializing in clinical drug development and medical innovation. He is the founder of Kirsch Dermatology in Naples, Florida and is also the Chief of Dermatology at the Naples Community Hospital. Kirsch Dermatology Website Dr. Kirsch started his career as a lawyer and holds law degrees from the University of Western Ontario (LL.B.) and Georgetown (LL.M. Securities and Financial Regulation). Dr. Kirsch completed his pre-medical studies at the University of Pennsylvania, medical school at Brown University, internship at the Mayo Clinic (Florida) and dermatology residency at the University of North Carolina. In partnership with the Mayo Clinic, he filed to patent a novel topical composition for the treatment of skin hyperpigmentation that he co-developed and also oversaw a successful pilot study of the formulation. Dr. Kirsch has experience with therapeutic drug development programs from pre-clinical to Phase 3 studies. He is licensed to practice medicine in California, Colorado, Florida, and North Carolina and law in New York and Ontario.

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