Several categories of medications can cause melasma or melasma-like dark patches on the skin, with hormonal contraceptives and anti-seizure drugs being the most well-documented triggers. About 17% of women with melasma trace the onset of their patches directly to starting oral contraceptives, making them one of the most common drug-related causes. Beyond hormonal medications, antibiotics, heart medications, pain relievers, and even certain cancer therapies can darken the skin in patterns that look identical to classic melasma.
Hormonal Contraceptives
Combined oral contraceptive pills, which contain both estrogen and a progestin, are the medication most commonly linked to melasma. Estrogen stimulates the pigment-producing cells in your skin to ramp up melanin output, especially when those cells are also exposed to UV light. The result is the symmetrical brown or grayish-brown patches on the cheeks, forehead, upper lip, or jawline that define melasma.
Other hormonal contraceptives can carry similar risk. Patches, vaginal rings, and hormonal IUDs that release a progestin have all been reported as triggers, though the association is strongest with pills that deliver estrogen orally. If you notice facial darkening after starting a new contraceptive, the timing is worth mentioning to your prescriber, because switching to a non-hormonal method sometimes allows the pigmentation to gradually fade.
Hormone Replacement Therapy
Postmenopausal women using hormone replacement therapy (HRT) face a similar risk, particularly with high-dose oral estrogen-only formulations. Case reports have documented melasma appearing not just on the face but also on the forearms in women with medium to dark skin tones (Fitzpatrick types III through VI). Combined oral and transdermal HRT formulations have also been implicated, though the evidence is thinner. Topical and vaginal HRT formulations have minimal reported association with melasma, which may make them a reasonable alternative for women who are concerned about skin changes.
Anti-Seizure Medications
Phenytoin, a widely used anticonvulsant, causes pigmentation resembling melasma in roughly 10% of people who take it. Unlike hormonal triggers, phenytoin works by acting directly on pigment-producing cells, causing them to spread melanin granules more aggressively and build up extra pigment in the outer layer of skin. The encouraging part: this pigmentation typically fades within a few months after the drug is stopped, which is faster than many other forms of melasma.
Antibiotics
Several antibiotics can trigger facial darkening that mimics melasma. Tetracyclines are among the most common culprits because they reduce the skin’s tolerance to UV light, making sun-exposed areas more vulnerable to pigment changes. Minocycline, a tetracycline-family drug often prescribed for acne or infections, is particularly well known for causing blue-gray or brown discoloration on the face and other sun-exposed skin.
Other antibiotics linked to skin pigmentation include metronidazole, clarithromycin, levofloxacin, sulfonamides, isoniazid (used for tuberculosis), and penicillin. The mechanism varies by drug, but a common thread is the generation of reactive oxygen species during the drug’s metabolism. These unstable molecules can stimulate melanin production in the skin, especially when combined with sun exposure.
Heart Medications
Amiodarone, prescribed for irregular heart rhythms, causes a distinctive skin discoloration in about 9% of younger patients on long-term treatment. The color is different from typical melasma: rather than brown patches, amiodarone tends to produce a slate-colored, blue-gray, or purple tint on sun-exposed areas. The discoloration depends on the total dose you’ve taken, how long you’ve been on the drug, and how much sun exposure you get. Up to 57% of people on amiodarone experience photosensitivity (sunburn-like reactions) early in treatment, which can precede the more lasting pigment changes.
Amiodarone-related pigmentation can be slow to resolve even after the drug is discontinued, partly because the medication and its byproducts accumulate in the skin over time.
Pain Relievers and Anti-Inflammatory Drugs
Nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen have both been documented as causes of drug-induced skin pigmentation. While these are among the most commonly used medications in the world, pigmentation as a side effect is uncommon. The risk increases with prolonged use and regular sun exposure. If you’re taking NSAIDs daily for a chronic condition and notice new facial darkening, the connection is worth exploring.
Cancer Therapies
Imatinib, a targeted cancer drug used for certain leukemias and other cancers, has been reported to cause melasma-like pigmentation predominantly on the forehead and cheeks. In a documented case series of five patients, the darkening appeared about three months after starting therapy. This is consistent with the drug’s effect on specific cellular pathways that also influence pigment-producing cells. Other chemotherapy and cytotoxic agents have been associated with skin pigmentation changes as well, though the patterns and colors vary widely depending on the specific drug.
Other Medications Linked to Pigmentation
The list of drugs capable of changing skin color is longer than most people expect. Additional categories include:
- Antidepressants and antipsychotics: Several psychiatric medications have been associated with skin darkening, particularly with long-term use.
- Anticoagulants: Blood thinners can occasionally contribute to pigmentation changes.
- Antimalarials: Drugs like chloroquine and hydroxychloroquine can cause blue-gray pigmentation, especially on the shins and face.
- Heavy metals: Medications containing silver, gold, or bismuth can deposit in the skin and create discoloration that looks similar to melasma but is caused by metal accumulation rather than excess melanin.
How Drug-Induced Melasma Differs
Melasma triggered by a medication can look identical to the more common forms caused by pregnancy or sun exposure alone. The key difference is the timeline. If dark patches appeared within weeks to months of starting a new drug, that connection matters. Drug-induced pigmentation sometimes shows up in slightly unusual locations (forearms, for instance, rather than just the face) or in atypical colors like blue-gray rather than brown, which can help distinguish it.
The most important practical distinction is that drug-induced melasma has a clearer path to improvement. When the triggering medication is stopped (or swapped for an alternative), the pigmentation often fades over the following months. Phenytoin-related darkening, for example, typically clears within a few months of discontinuation. Hormonal melasma from contraceptives can take longer and may not fully resolve on its own, but it generally improves. Amiodarone pigmentation tends to be the most stubborn because the drug lingers in tissues long after you stop taking it.
Regardless of the trigger, sun protection is the single most effective way to prevent drug-induced melasma from worsening. UV exposure amplifies every medication-related pigmentation pathway, so consistent broad-spectrum sunscreen use and sun avoidance make a real difference in both prevention and recovery.