Vonoprazan Linked to Bright Yellow Fluorescent Urine in Clinical Trial Participant

During a Phase I trial in Shanghai, a 25‑year‑old woman took a single 20 mg oral dose of a study drug and soon produced urine that fluoresced bright yellow under ordinary room lighting, visible without UV illumination.

The agent was vonoprazan fumarate (brand name Voquezna), a potassium‑competitive acid blocker. The participant remained asymptomatic and all routine laboratory values remained within normal limits. The fluorescence vanished after the drug was cleared and re‑appeared when dosing was restarted, as documented in a case report authored by Lei Sheng and Xuening Li from the Department of Clinical Pharmacology at Zhongshan Hospital, Fudan University.

Fluorescent Urine Usually Signals a Serious Problem

Fluorescent urine is classically linked to ethylene glycol poisoning—antifreeze often contains the dye sodium fluorescein—and to porphyria, a group of metabolic disorders in which porphyrins are excreted and fluoresce under ultraviolet light. Both conditions are normally identified with a Wood’s lamp. In this case, however, the fluorescence was visible under ambient room lighting, a feature the authors highlighted as particularly alarming because it does not require a special light source.

Eleven Days in a Controlled Ward Ruled Out Other Causes

Phase I study units provide a highly controlled environment that makes unusual observations more likely. The participant received a single 20 mg oral dose on day 1, followed by pharmacokinetic sampling for 48 h, then twice‑daily 20 mg doses until a final dose on day 9; she was discharged on day 11. She adhered to a standardized diet and took no other medications. Laboratory testing on days 3, 9, and 11 showed normal or clinically insignificant results. Urinalysis revealed a yellow to mild‑yellow color with normal pH, specific gravity, urobilinogen and no bilirubin. Urine output remained within the normal range and the participant reported no discomfort at any point, including a telephone follow‑up on day 18.

Using the Naranjo Adverse Drug Reaction Probability Scale, the investigators assigned a score of 8, which denotes a “probable” relationship between the drug and the observed effect. The calculation considered the temporal relationship to dosing, disappearance during drug washout, recurrence upon rechallenge, and the exclusion of dietary or concomitant medication influences, as well as direct visual verification. The parent Phase I trial was sponsored by Takeda Development Center Asia; the case authors reported no personal financial conflicts and received no separate funding for the manuscript.

Chemistry the Authors Believe Underlies the Glow

Vonoprazan is a pyrrole derivative that contains a benzene ring and several unsaturated bonds. Such conjugated aromatic systems can absorb light and re‑emit it at a longer wavelength—a phenomenon known as fluorescence. The authors hypothesize that either vonoprazan itself or one of its metabolites is responsible for the glowing urine, although no spectroscopic analysis was performed to confirm the mechanism. Individual factors such as genetic variations in the metabolizing enzymes CYP2C19 and CYP3A4, as well as renal clearance rates, may modulate the intensity of the effect. It remains unknown whether this is a common adverse effect or an isolated occurrence.

A Drug Now Approved and Widely Prescribed in the United States

Vonoprazan fumarate (Voquezna) has moved beyond experimental use. It is the first potassium‑competitive acid blocker approved in the United States and, according to a federal review, the first novel class of gastric‑acid medication approved in three decades. The FDA initially approved the tablets for healing and maintaining healing of erosive esophagitis of all grades and for associated heartburn relief, as well as in combination regimens for Helicobacter pylori infection. A later expansion approved a 10‑mg dose for heartburn in non‑erosive reflux disease, a condition estimated to affect roughly 45 million U.S. adults.

Drug‑induced urine discoloration is a recognized phenomenon. Rifampin can produce red‑orange urine, methylene blue yields blue‑green, nitrofurantoin may turn urine brown to black, and high doses of riboflavin cause a mild yellow fluorescence. The case authors argue that vonoprazan should be added to this list, because a striking visual change in an otherwise well patient can trigger unnecessary invasive testing and anxiety. Their guidance is aimed at clinicians: a sudden, dramatic urine color change merits discussion with the prescriber, but patients should not discontinue the medication without professional advice. In this instance, the participant was asymptomatic, had normal renal and hepatic function, and the fluorescence resolved spontaneously after the drug was cleared.

Key Questions Answered

What drug caused the fluorescent urine?

Vonoprazan fumarate (brand name Voquezna), a potassium‑competitive acid blocker used to suppress stomach acid.

Was the participant harmed?

No. She remained asymptomatic, had normal urine output and laboratory results, and the fluorescence resolved on its own after the drug cleared.

Why is fluorescent urine normally concerning?

It has historically been linked to ethylene glycol poisoning (antifreeze dye) and porphyrias—conditions typically identified under ultraviolet light.

How confident are the authors that the drug caused it?

They assigned a probable rating (Naranjo score 8) based on timing, resolution during washout, recurrence with repeat dosing, and exclusion of dietary or medication confounders.

Should patients on vonoprazan expect this?

The frequency is unknown; this is a single case. Any notable urine color change should be reported to the prescriber, but the medication should not be stopped independently.

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