What Drug Makes Your Eyes Yellow? A Look at Medications

Several classes of prescription drugs can cause yellowing of the eyes, a condition doctors call scleral icterus. The common thread is bilirubin, a yellow pigment the body produces when it breaks down old red blood cells. When a medication interferes with how your liver processes or excretes bilirubin, the pigment builds up in your blood and stains the whites of your eyes. The list of culprits is longer than most people expect, stretching from HIV medications and antibiotics to tuberculosis drugs, anabolic steroids, and even herbal supplements marketed as harmless.

Why Bilirubin Goes to Your Eyes First

Bilirubin has a strong affinity for elastin, the stretchy protein concentrated in the tissue of your sclera (the white outer coat of the eye). That is why the eyes often turn yellow before the rest of the skin does, and why a doctor checking for jaundice will pull down your lower eyelid or ask you to look up. Normally, the liver converts bilirubin into a water-soluble form and dumps it into bile, which leaves the body through the digestive tract. Anything that disrupts this chain, whether by damaging liver cells, blocking bile flow, or overwhelming the liver’s processing capacity, can push bilirubin levels high enough to color your eyes.

Drugs cause yellow eyes through three broad mechanisms. Some directly injure liver cells (hepatocellular damage), releasing enzymes and impairing the organ’s ability to clear bilirubin. Others block the tiny bile ducts inside the liver, a pattern called cholestasis, which traps bilirubin like a clogged drain. A third group interferes with a specific enzyme that conjugates bilirubin without necessarily damaging the liver at all. Knowing which mechanism is at work matters because it determines how serious the problem is and what happens when you stop the drug.

HIV Medications and the Enzyme They Block

Atazanavir, a protease inhibitor widely used in HIV treatment, is one of the best-known causes of drug-related yellow eyes. It works by directly inhibiting UGT1A1, the liver enzyme responsible for converting bilirubin into a form the body can excrete. Lab studies showed that atazanavir blocks this enzyme through a mixed-type inhibition mechanism, and a related HIV drug, indinavir, does the same thing, though far less potently.¹ The result is a rise in unconjugated bilirubin in the blood, which stains the eyes yellow even though the liver itself is not being damaged.

This is an important distinction. With atazanavir, jaundice is essentially cosmetic. The liver enzymes that signal real liver injury (ALT, AST) stay normal. The yellowing reverses once the drug is stopped or the dose is adjusted. But “cosmetic” does not mean it has no consequences. A study at an HIV clinic in Kampala, Uganda, found that patients who developed visible jaundice while on boosted atazanavir had nearly three times the odds of poor adherence to their entire antiretroviral regimen, even after adjusting for factors like stigma and alcohol use.² People who look sick sometimes decide to stop taking the pills that make them look sick, which in the case of HIV treatment can have devastating consequences. Clinicians who prescribe atazanavir generally counsel patients about the yellowing upfront so it does not come as a shock.

Antibiotics That Can Damage the Liver

Amoxicillin-clavulanate (sold as Augmentin and generic equivalents) is one of the most commonly prescribed antibiotics in the world, and it is also one of the most frequent antibiotic causes of drug-induced liver injury. The clavulanate component, added to broaden the drug’s effectiveness, is thought to be the main offender. In one documented case, a patient who took the combination for six weeks developed cholestatic jaundice with a total bilirubin level well over ten times normal.³ The liver injury from amoxicillin-clavulanate typically follows a cholestatic pattern, meaning bile flow is blocked rather than liver cells being destroyed outright. Recovery usually happens after the drug is stopped, but it can take weeks to months for bilirubin to normalize and the yellow tinge to fade.

Other antibiotics can raise bilirubin through entirely different pathways. Ceftriaxone, a powerful injectable antibiotic in the cephalosporin family, does not injure the liver but competes with bilirubin for binding spots on albumin, the main transport protein in blood. When ceftriaxone bumps bilirubin off albumin, the freed bilirubin can reach tissues it would otherwise not, raising the risk of jaundice. Research on blood samples from jaundiced newborns showed that even at concentrations achieved during standard dosing, ceftriaxone produced a measurable increase in free bilirubin.⁴ A separate study confirmed that the antibiotic directly displaces bilirubin from albumin-binding sites.⁵ This effect is most dangerous in newborns, whose brains are vulnerable to high free-bilirubin levels, and is the reason ceftriaxone carries a caution against use in jaundiced infants.

Tuberculosis Drugs

The standard regimen for tuberculosis includes isoniazid and rifampicin, and both drugs can cause liver toxicity that leads to jaundice. Isoniazid is associated with elevated liver enzymes and rising bilirubin, while rifampicin adds its own liver-damaging potential through immune-allergic reactions and a similar pattern of elevated enzymes and bilirubin.⁶ When given together, which is how TB is almost always treated, the risk compounds. Animal and cell studies have demonstrated that the combination triggers inflammatory responses and oxidative stress in liver tissue, activating a cascade that damages hepatic cells.⁷

TB treatment typically lasts at least six months, and patients are monitored with periodic blood tests specifically because liver problems can develop at any point during the course. When jaundice appears, doctors face a difficult balancing act: stopping the drugs lets an active TB infection potentially worsen, but continuing them risks progressive liver failure. The usual approach is to halt treatment temporarily, let the liver recover, and then reintroduce the drugs one at a time to identify which agent the patient cannot tolerate.

Anabolic Steroids

Oral anabolic steroids, particularly the 17-alpha-alkylated varieties favored in bodybuilding, are a well-documented cause of severe cholestatic jaundice. The alkyl group that makes these steroids survive the digestive tract also makes them toxic to the liver’s bile-transport system. In one reported case, a bodybuilder who used a regimen containing stanozolol and testosterone propionate for eight weeks developed jaundice so severe that his total bilirubin reached over 41 mg/dL, roughly twenty times the upper limit of normal.⁸ At that level, the bilirubin overload had begun damaging the kidneys as well, requiring plasma exchange to physically remove the pigment from the blood.

Steroid-induced cholestasis has a reputation for being slow to resolve. Even after stopping the drugs, jaundice can persist for months because the bile-transport machinery of the liver takes time to recover. Many users do not disclose steroid use to their doctors, which means the diagnosis is sometimes delayed while clinicians pursue other explanations for the jaundice. If you develop yellow eyes and are using any form of anabolic steroid, telling your doctor is critical for getting the right workup.

Psychiatric and Seizure Medications

Anticonvulsants, antidepressants, and antipsychotics can all cause liver injury, though this is relatively rare compared to other drug categories.⁹ Valproic acid (used for seizures and bipolar disorder) is probably the best-known offender in this group, capable of causing hepatocellular damage that raises bilirubin. Certain antipsychotics, especially chlorpromazine, have a longstanding association with cholestatic jaundice. Among antidepressants, liver injury has been documented with a range of agents, though it typically shows up as elevated liver enzymes rather than frank jaundice.

The rarity of severe liver events with psychiatric drugs means that routine liver monitoring is not standard for most of them, which can catch patients off guard. If you are on a long-term psychiatric medication and notice your eyes turning yellow, it warrants an urgent call to your prescriber, but keep in mind that the statistical likelihood of it being your antidepressant or antipsychotic is low compared to other causes of jaundice.

Herbal Supplements and Green Tea Extract

One of the more surprising causes of drug-induced yellow eyes comes from products that people take voluntarily for health or weight loss. Herbal and dietary supplements are a growing source of liver injury, and green tea extract (GTE) is one of the most frequently implicated ingredients. Data from a large prospective registry of drug-induced liver injuries found that many supplement-related cases involved products containing catechins, the active compounds in green tea. Strikingly, about half of the tested products that contained GTE-related catechins were not even labeled as containing green tea extract.¹⁰ Patients typically developed an illness resembling acute hepatitis within one to three months of starting the product. While most recovered after stopping the supplement, fatal cases were reported in up to about one in ten patients who presented with acute liver injury and jaundice.

The difficulty with supplements is that they are not regulated with the same scrutiny as prescription drugs, and ingredient labels are often incomplete or inaccurate. A person who develops yellow eyes may not even think to mention a “natural” supplement to their doctor. If you are taking any herbal product and your eyes start to look yellow, bring the bottle in with you.

Drugs That Destroy Red Blood Cells Instead of Hurting the Liver

Not all drug-induced jaundice originates in the liver. Some medications cause the immune system to attack red blood cells, a process called drug-induced immune hemolytic anemia. When red blood cells are destroyed faster than the liver can clear the resulting bilirubin, levels spike and the eyes turn yellow. A case report documented this happening with dapagliflozin, a diabetes drug in the SGLT2 inhibitor class, which triggered extravascular hemolysis with a clear rise in indirect (unconjugated) bilirubin, elevated markers of red cell destruction, and decreased haptoglobin.¹¹ Other drugs historically linked to immune hemolytic anemia include certain penicillins, cephalosporins, quinidine, and methyldopa.

The clinical clue that hemolysis rather than liver damage is causing the jaundice is the type of bilirubin that rises. Unconjugated (indirect) bilirubin goes up when the problem is red blood cell destruction, whereas conjugated (direct) bilirubin rises when the liver itself or the bile ducts are the issue. A simple blood panel can distinguish between the two, which changes the treatment approach entirely.

When Your Genes Make a Drug More Likely to Turn Your Eyes Yellow

Gilbert syndrome is an inherited condition affecting roughly 5 to 10 percent of the population in which the UGT1A1 enzyme works at reduced capacity. People with Gilbert syndrome have mildly elevated bilirubin at baseline and often never know about it unless a blood test picks it up incidentally. But when these individuals take a drug that further stresses bilirubin metabolism, the combined effect can push bilirubin high enough to cause visible jaundice. In patients with certain cancers undergoing chemotherapy, for instance, concurrent Gilbert syndrome leads to unconjugated hyperbilirubinemia because the already-sluggish enzyme cannot keep up with the demands placed on it.¹²

This has practical implications for cancer treatment. Irinotecan, a chemotherapy drug used for colorectal and other cancers, is partly cleared through bile. In patients with existing liver impairment, drug exposure goes up because biliary excretion drops.¹³ For someone who also carries the Gilbert syndrome variant, the margin for safe dosing shrinks further. Pharmacogenomic testing for UGT1A1 status before starting irinotecan is now recommended in clinical guidelines to help calibrate the dose and reduce the chance of severe toxicity.

Gilbert syndrome also amplifies the jaundice caused by atazanavir. The drug inhibits the same enzyme that Gilbert syndrome already impairs, so the double hit produces noticeably higher bilirubin levels than either factor alone. If you carry the Gilbert variant and are prescribed atazanavir, your doctor may choose an alternative antiretroviral or at least prepare you for more pronounced yellowing.

Yellow Skin That Spares the Eyes

Not every yellow discoloration is jaundice. Carotenemia, caused by high intake of beta-carotene from foods like carrots, sweet potatoes, and certain supplements, turns the skin yellow-orange but characteristically does not affect the sclera.¹⁴ If someone’s palms and soles look yellow but the whites of their eyes are still white, carotenemia is the likely explanation, and it is harmless. The distinction matters because a misdiagnosis of jaundice can trigger an expensive and anxiety-producing workup for liver disease.

Some tanning agents and self-tanning lotions containing dihydroxyacetone can also give the skin a yellowish cast. Again, the eyes will be spared. The quick bedside test remains the same one doctors have used for generations: check the sclera. If the white of the eye is yellow, bilirubin is the problem, and a medication or underlying condition needs to be investigated.

How Doctors Gauge the Seriousness of Drug-Induced Jaundice

Not all drug-induced jaundice carries the same risk. A concept called Hy’s Law (named after the late hepatologist Hyman Zimmerman) holds that when a drug causes both significant liver-cell damage and a rise in bilirubin, the chances of a fatal outcome jump sharply. A recent refinement of this principle using a large database of drug-induced liver injury cases found that when the pattern of injury was hepatocellular (meaning the liver cells themselves were damaged, not just bile flow blocked), mortality was about 11 percent, compared to roughly 2 percent when the injury followed a cholestatic or mixed pattern.¹⁵ That is a stark difference: the same yellow eyes can mean very different things depending on which liver tests are elevated alongside the bilirubin.

Researchers have also explored whether very high liver enzyme levels without jaundice carry a similar warning. The relationship turns out to be less straightforward, with elevated enzymes alone being a less reliable predictor of bad outcomes than the combination of enzyme elevation plus jaundice.¹⁶ For a patient, the practical takeaway is that yellow eyes accompanied by fatigue, dark urine, and abdominal pain warrant an urgent visit, not a wait-and-see approach.

What Happens After You Stop the Drug

For most medications that cause jaundice, stopping the offending drug is the primary treatment, and the yellowing gradually resolves. The timeline varies considerably. Atazanavir-related jaundice can fade within days because no actual liver damage occurred. Cholestatic injuries from antibiotics like amoxicillin-clavulanate may take weeks to months. Steroid-induced cholestasis is sometimes among the slowest to clear.

Re-exposure is dangerous with many of these drugs. In a documented case involving liraglutide (a GLP-1 receptor agonist used for diabetes and weight management), a patient’s liver enzymes dropped back to normal after the drug was stopped. When liraglutide was restarted, liver enzymes shot up dramatically within ten days, with ALT reaching over 1,200 U/L, confirming the drug as the cause.¹⁷ After permanent discontinuation, enzymes normalized over the following month. This kind of “rechallenge” is sometimes done deliberately (under close monitoring) to confirm a diagnosis, but it is not something to try on your own by restarting a medication you think caused a problem.

If you develop yellow eyes while on any medication, your doctor will typically order a liver panel to measure bilirubin (total and direct), ALT, AST, and alkaline phosphatase. The pattern of those results, combined with the timing of your medication use, usually points clearly to the cause. In ambiguous cases, imaging of the liver and bile ducts or a liver biopsy may be needed to rule out other conditions like gallstones, viral hepatitis, or an underlying liver disease that was unmasked by the drug rather than caused by it. Keeping a complete and honest medication list, including supplements and anything obtained without a prescription, makes this detective work considerably faster.