Rifampin’s Strangest Side Effects

November 23, 2025

Monique Nguyen

Fountain Valley High School

12th Grade

Have you ever had your pee turn bright orange? It’s not uncommon. In the United States, it’s estimated that almost 13 million people live with a dormant version of one of the most prevalent epidemic diseases in history: tuberculosis (TB). Rifampin is a primary antibiotic treatment, but it yields several unique side effects as well.

Predominantly caused by active reproduction of the bacterium Mycobacterium tuberculosis, active TB is exceptionally dangerous with relatively easy transmission—the germs are airborne and attach to microscopic drop particulates from a diseased person’s cough or singing. The disease mainly affects the lungs, but it may also affect other or multiple parts of the body as well. Contracting active TB may be evident through symptoms like night sweats, weight loss, persistent/painful cough, or coughing blood or phlegm (more specifically, sputum), among others. Untreated, TB is fatal. But, through modern antibiotic treatments such as rifampin, active cases in the United States have lowered. 

Latent TB, a stage after the initial primary infection of TB, may be more common. The bacterium remains within the body, but immune cells build walls around it to prevent it from reproducing further. The bacterium therefore survives but lies dormant, and the carrier exhibits no apparent symptoms and cannot spread the bacterium. However, it is possible for latency to become active in the immunocompromised. Testing for TB is most common through skin-prick tests, which yield positive for both latent and active TB; once tested positive, chest x-rays and blood tests are used to confirm the presence and stage of the disease.

The therapeutic rifampin is an antibiotic used to treat primarily TB cases and other illnesses, such as those from uncommon mycobacteria infections. It can be used in conjunction with other therapies, such as pyrazinamide and isoniazid, which are common prescriptions for TB. Rifampin works by acting as an inhibitor for DNA-dependent RNA polymerase (RNAP). It prohibits RNA synthesis by forming hydrogen bonds with the proteins’ amino acids using its four hydroxyl groups, blocking the active site of RNA and disrupting the formation of a phosphodiester linkage at its 5’ end. Rifampin prevents further elongation with short (two to three nucleotides) RNA transcripts. 

Dosages and treatment length vary by type of infection, but generally, it follows an oral route and is well absorbed in the gastrointestinal tract. The drug itself is a rifamycin derivative, a partly synthetic class of antibiotics synthesized by the bacterium Amycolatopsis rifamycinica. As a polyketide, its molecules have a naphthoquinone chromophore core—a specific molecular structure—responsible for its characteristic reddish-orange color. As rifampin passively diffuses throughout the body, it reaches cerebral spinal fluid, urine, sweat, tears, saliva, sputum, and more; these bodily fluids are temporarily stained a red-orange color. For this reason, it’s common for rifampin to result in orange urine, discolored teeth, and even orange tears permanently staining contact lenses. This side effect is harmless and may even fade over time; just think of it as an indicator that rifampin is widely distributed within the body. 

Eating should be avoided right before medication to maximize absorption. If used in combination with isoniazid, consumption of certain foods may be advised for limitation, but alcohol is the only food that should be avoided during intake of rifampin itself, particularly if used in conjunction with other hepatotoxic drugs. The chief reason for this is because the medication has a history, though uncommon, of liver damage and disease. Asymptomatically, serum bilirubin levels may increase, which indicates poor bilirubin—a waste product from old, broken-down red blood cells—removal and can lead to jaundice, among other effects. Another temporary effect is an increase in serum aminotransferase levels, which are enzymes primarily located in the liver that are responsible for metabolizing amino acids, so this can be particularly dangerous if one’s liver cells are inflamed or damaged and these enzymes leak into the blood. Cholestasis may also occur if the drug causes bile buildup in the liver.

There may be several other side effects that may or may not require medical attention, including but not limited to heartburn, nausea, diarrhea, fever, allergic reactions, rash, and even bleeding. Consulting with one’s medical caretaker is always best to ensure safe treatment, especially with a condition as serious as TB. Still, after taking rifampin for the first time, hopefully the orange pee isn’t too heart-stopping of a surprise!