Oral vs. topical medication—which works better? Understanding how to choose internal and external medications for melasma and acne

The difference between oral and topical medications is whether they work throughout the body or directly at the site of application. For melasma (light brown spots spreading across the cheeks and other areas), there is a summary of research showing improvement with the oral medication tranexamic acid, and combination use with topical medications has also been studied[1][2]. Which is suitable depends on the type of concern, any existing conditions or medications you are taking, and your skin sensitivity.

What is the difference between oral and topical medications?

Even with the same ingredient, how it works and precautions differ depending on whether it is taken orally or applied topically. For example, tranexamic acid comes in oral, topical, and injectable forms, and is used both alone and in combination with other treatments[3].

Because oral medications reach the entire body, concerns about blood clots have been discussed regarding tranexamic acid[4]. Topical medications are barely absorbed by the body, so they are considered safer and easier to use.[4].

Does oral medication work better for melasma?

Based on current research, oral medication shows clearer effectiveness. A study reviewing 28 comparative trials found that oral tranexamic acid clearly lowered melasma severity scores at 8 and 12 weeks[1].

In the same review, topical tranexamic acid and tranexamic acid injected into the skin showed no clear difference[1]. However, the variation between studies is large, so it cannot be concluded that topical medication is ineffective.[1].

What happens when oral and topical medications are used together?

Combination use has been reported to improve results more readily than topical medication alone. In a 50-person comparative trial, the group that added oral tranexamic acid to a 4% hydroquinone topical cream and sunscreen showed a 55% decrease in melasma scores after 3 months[2]. The group that took a placebo instead of oral medication showed a 10.9% decrease[2].

Three months after stopping the medication, the combination group remained 42% lower than baseline[2]. The placebo group was 4.7% lower[2]Because melasma tends to recur, it is important to discuss the course after discontinuation.

What is the difference between topical medications?

With topical medications, selection is based on balancing efficacy and skin irritation. In a 99-person comparative trial, a cream containing tranexamic acid and niacinamide improved melasma as much as a 4% hydroquinone cream[5].

Adverse effects occurred in 18.18% of the hydroquinone group (approximately 18 per 100 people)[5]. In the tranexamic acid cream group, both groups had rates of 3.03% (approximately 3 per 100 people), and recurrence was observed in the hydroquinone group[5]. Textbooks describe combining topical retinoids or hydroquinone with peeling as a treatment approach for melasma[6].

How should oral and topical medications be combined for acne?

For acne, topical retinoids (medications that prevent pore clogging) form the foundation of treatment[7]. A combination of benzoyl peroxide gel in the morning and retinoid at night is commonly used[7].

When using oral antibiotics, combination with topical retinoids and similar medications is recommended[7]. People using retinoids should pay attention to the break period and skin sensitivity before procedures such as peeling[8].

How do I decide which medication is right for me?

Three guidelines to consider when deciding:

Type of concern: melasma, other spots, or acne[1][7]

Body condition: any history of blood clot-related conditions or other medications being taken[4]

Skin condition: does redness or irritation appear easily with topical medications, or are there procedure plans[5][8]

What should be confirmed during examination?

Which medication is appropriate cannot be determined from an article alone. It is necessary to confirm during examination whether the spots are melasma or something else, and whether your body is in a condition that allows oral medication use.

During examination, tell your doctor about your current conditions and medications you are taking, and discuss how long to continue treatment and how to monitor after stopping.